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Experts debate low-carb diets for people with diabetes
It’s an ongoing debate in the diabetes world: Is it ideal to consume a very-low-carbohydrate diet, or is it better to go with moderate amounts of healthful carbs?
At the annual scientific sessions of the American Diabetes Association, Carol F. Kirkpatrick, PhD, RDN, spoke first, arguing in favor of diets consisting of moderate, high-quality carbohydrates.
Dina Hafez Griauzde, MD, countered that very-low-carbohydrate diets are more beneficial for people with diabetes, primarily type 2 diabetes.
Both speakers based their arguments on published evidence but agreed in the end that discussion with patients about individual dietary preferences should play a major role in the ultimate decision.
Moderate-carbohydrate eating is best
Dr. Kirkpatrick began by explaining that definitions of “low carb” vary in the literature, which makes comparisons between studies difficult. On the basis of a 2019 review that she coauthored, “moderate” carbohydrate consumption was defined as a diet in which 26%-44% of total daily calories are from carbohydrates. “Low” carbohydrate consumption was defined as a diet in which 10%-25% of calories were from carbohydrates. Consuming less than 10% was defined as a very-low-carbohydrate diet (i.e., a ketogenic diet).
Across studies, she noted, the literature shows that within the first 6 months weight loss is typically greater with carbohydrate-restricted diets than with higher-carbohydrate diets, but that by 1 year and beyond weight loss is similar.
“That can be partly due to the difficulty in people maintaining that very severe dietary restriction, although ... we can all acknowledge that it’s difficult for patients to adhere to any dietary pattern, so for sure by 12 months, the difference in the weight loss is gone between the two,” said Dr. Kirkpatrick, of Midwest Biomedical Research, Pocatello, Idaho.
In a recent meta-analysis of 35 trials that examined the dose-dependent effects of carbohydrate restriction for patients with type 2 diabetes, there was a significant decrease in weight as carbohydrates were reduced. But by 12 months (17 trials), the greatest weight reduction was seen at 35% carbohydrate intake.
“It may just be that people were able to adhere to that moderate intake better,” she explained.
Regarding lipids, in her 2019 review and in several meta-analyses since, the effects on low-density lipoprotein cholesterol (LDL-C) varied. For some patients, adhering to a low-carb diet led to reductions in LDL-C, especially if the participants also lost weight, whereas in other patients, a low-carb diet led to an increase in LDL-C.
Either way, a high intake of saturated fatty acids is key to an increase in LDL-C, Dr. Kirkpatrick noted. “So, it’s important that, if a patient chooses to follow a very low carbohydrate diet or any kind of dietary pattern that restricts carbohydrate, that they replace the carbohydrate with unsaturated fat and not saturated fatty acid foods to avoid that increase in LDL-C.”
Generally, the evidence also shows that carbohydrate restriction typically leads to lower triglyceride levels and higher high-density lipoprotein (HDL) cholesterol levels. However, the same meta-analysis showed that the greatest reduction in LDL-C occurred at about 40% carbohydrate consumption.
Another recent meta-analysis showed that LDL-C rose significantly by an average 12.4 mg/dL with very-low-carb (3%-30%) diets, but only slightly, by 0.4 mg/dL, with moderate carb (40%-45%) intake.
Consuming very-low-carb diets did lead to greater reductions in triglycerides, compared with consuming moderate carb diets (23.9 mg/dL vs. 8.9 mg/dL).
“However, in terms of cardiovascular health, we are not entirely sure what that means. ... We have to look at the overall results in the presence of both triglyceride lowering as well as LDL cholesterol,” Dr. Kirkpatrick noted.
Carbohydrate restriction did consistently lead to lower hemoglobin A1c levels by an average of 0.4, 0.6, and 1.0 percentage points at 6 months for diets of 40%, 30%, and 15% carbohydrate, respectively. However, by 12 months, the effect had waned to 0.15, 0.2, and 0.4 A1c percentage points.
“Again, carbohydrate restriction, especially severe, is difficult for people to adhere to, and moderate carbohydrate intake would allow our patients to consume an appropriate amount of carbohydrate and still achieve improved glycemic control,” Dr. Kirkpatrick said.
Two large randomized controlled trials – PREDIMED and CORDIOPREV – examined the effects of the Mediterranean diet on cardiovascular disease prevention. Both showed a decrease in cardiovascular events with the Mediterranean diet, which involves consuming moderate amounts of carbohydrates.
“The Mediterranean dietary pattern has the strongest evidence for benefit, and it’s moderate in carbohydrates,” she concluded.
Very-low-carbohydrate eating is best
Dr. Griauzde was a last-minute replacement speaker for William S. Yancy Jr, MD, of Duke University, Durham, N.C., and presented his slides. She argued that consuming a very low carb diet improves glycemia and that it does not increase but possibly lowers cardiovascular risk.
She began by noting that prior to the discovery of insulin very-low-carb diets had been consumed for over a century to prolong life for people with type 1 diabetes.
“We have long recognized the deleterious role of carbohydrate in type 1 diabetes management, and we have increasingly recognized that role in the management of type 2 diabetes,” said Dr. Griauzde of the University of Michigan in Ann Arbor.
In a small study that compared maintaining a very-low-carb diet for 2 weeks with maintaining a high-carb diet for 2 weeks, total glucose areas under the curve were substantially lower (P < .05) during the low-carb phase, while A1c levels dropped from 7.3% to 6.8% (P = .006).
“We don’t see those outcomes with meds,” Dr. Griauzde noted, adding, “A diet very low in carbohydrates is one of the most potent tools we have to help our patients achieve glycemic control.”
Dr. Griauzde said that the carbohydrate-insulin model provides an explanation for why dietary carbohydrates are particularly obesogenic and metabolically harmful. That model contrasts with the energy balance model, which suggests that all calories are equal.
The rationale of the carbohydrate-insulin model is that dietary carbohydrate – either sugar or starch – raises serum glucose and insulin levels. A carbohydrate-restricted diet therefore reduces the dietary contribution to serum glucose, which then results in lower insulin levels. Insulin is a potent stimulator of lipogenesis (fat storage), and it is a potent inhibitor of lipolysis (the burning of fat). By lowering insulin levels, stored body fat is burned, serum ketone levels increase, and body weight is lowered.
This model suggests that, when insulin levels are chronically high because of excess carbohydrate consumption, circulating fuels are lowered, which leads to an increase in hunger and to overeating. This was demonstrated in a study that compared different levels of isocaloric glycemic index diets in 12 teenage boys with overweight or obesity. The higher-carbohydrate meals led to higher glucose and insulin levels and more food consumption.
In a systematic review of 13 trials of restricted-carbohydrate diets (< 45% carbohydrates) for adults with diabetes, the degree of improvement in A1c level correlated with the degree of carbohydrate restriction over 2-26 weeks (P = .013).
And in a network meta-analysis of 56 trials that compared nine diets among a total of 4,937 participants with type 2 diabetes, one conclusion was that “for reducing A1c, the low-carbohydrate diet was ranked as the best dietary approach (SUCRA: 84%), followed by the Mediterranean diet (80%), and Paleolithic diet (76%), compared with a control diet.”
Regarding the criticism that very-low-carbohydrate diets are high in saturated fat and therefore raise the risk of cardiovascular disease, Dr. Griauzde pointed to another meta-analysis of 21 prospective studies with more than 300,000 participants with 5-25 years of follow-up. In that analysis, the intake of saturated fat was not associated with an increased risk of cardiovascular disease or stroke.
Furthermore, a 12-week randomized controlled trial that involved 40 adults with overweight also suggested that a very-low-carb diet may be superior to a low-fat diet in improving aspects of the metabolic syndrome, including body mass index, lipid levels, and insulin sensitivity. Small LDL particles, which are more atherogenic than larger LDL particles, also decreased despite a threefold increase in saturated fat intake.
Rebuttals: Overall diet, patient preference matter
During the rebuttals, Dr. Kirkpatrick pointed out that large LDL particles are also atherogenic. In addition, she noted that the studies that showed that saturated fat isn’t associated with cardiovascular disease didn’t consider the macronutrients that replaced the saturated fat.
“It really is about increasing consumption of foods that we know are associated with cardiovascular benefit, including plant-based foods that are high quality and not refined carbohydrates ... and healthy protein sources. ... Hopefully we can step away from just looking at macronutrients and look at the total amount of food that people are choosing to eat.”
Importantly, Dr. Kirkpatrick said, patients need to be asked about their current dietary patterns and preferences. “Interventions should be patient centered and sensitive to cultural differences. Personalized lifestyle interventions increase the likelihood of success.”
Dr. Griauzde pointed out that newer antiobesity drugs can be added to any diet to decrease appetite and enhance adherence.
Dr. Griauzde also observed, “We can label a very-low-carbohydrate diet ‘extreme,’ but maybe, from the patient’s perspective, it’s extreme to take 200 units of insulin a day. If you can give them the opportunity to discontinue use of the insulin by following a very-low-carbohydrate dietary pattern, that is the opportunity that our patients deserve to have.”
But overall, she agreed with Dr. Kirkpatrick about individualizing any dietary approach: “We will never know from any of the trials that have been done or that will be done in the future what diet is best for an individual patient. ... Our job is to help our patients find the dietary approach that works best for them.”
Dr. Kirkpatrick is a clinical scientist with Midwest Biomedical Research, which has received funding from various food and pharmaceutical companies. She has not received any direct funding. Dr. Yancy is a consultant for The Simply Good Foods Co. Dr. Griauzde has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
It’s an ongoing debate in the diabetes world: Is it ideal to consume a very-low-carbohydrate diet, or is it better to go with moderate amounts of healthful carbs?
At the annual scientific sessions of the American Diabetes Association, Carol F. Kirkpatrick, PhD, RDN, spoke first, arguing in favor of diets consisting of moderate, high-quality carbohydrates.
Dina Hafez Griauzde, MD, countered that very-low-carbohydrate diets are more beneficial for people with diabetes, primarily type 2 diabetes.
Both speakers based their arguments on published evidence but agreed in the end that discussion with patients about individual dietary preferences should play a major role in the ultimate decision.
Moderate-carbohydrate eating is best
Dr. Kirkpatrick began by explaining that definitions of “low carb” vary in the literature, which makes comparisons between studies difficult. On the basis of a 2019 review that she coauthored, “moderate” carbohydrate consumption was defined as a diet in which 26%-44% of total daily calories are from carbohydrates. “Low” carbohydrate consumption was defined as a diet in which 10%-25% of calories were from carbohydrates. Consuming less than 10% was defined as a very-low-carbohydrate diet (i.e., a ketogenic diet).
Across studies, she noted, the literature shows that within the first 6 months weight loss is typically greater with carbohydrate-restricted diets than with higher-carbohydrate diets, but that by 1 year and beyond weight loss is similar.
“That can be partly due to the difficulty in people maintaining that very severe dietary restriction, although ... we can all acknowledge that it’s difficult for patients to adhere to any dietary pattern, so for sure by 12 months, the difference in the weight loss is gone between the two,” said Dr. Kirkpatrick, of Midwest Biomedical Research, Pocatello, Idaho.
In a recent meta-analysis of 35 trials that examined the dose-dependent effects of carbohydrate restriction for patients with type 2 diabetes, there was a significant decrease in weight as carbohydrates were reduced. But by 12 months (17 trials), the greatest weight reduction was seen at 35% carbohydrate intake.
“It may just be that people were able to adhere to that moderate intake better,” she explained.
Regarding lipids, in her 2019 review and in several meta-analyses since, the effects on low-density lipoprotein cholesterol (LDL-C) varied. For some patients, adhering to a low-carb diet led to reductions in LDL-C, especially if the participants also lost weight, whereas in other patients, a low-carb diet led to an increase in LDL-C.
Either way, a high intake of saturated fatty acids is key to an increase in LDL-C, Dr. Kirkpatrick noted. “So, it’s important that, if a patient chooses to follow a very low carbohydrate diet or any kind of dietary pattern that restricts carbohydrate, that they replace the carbohydrate with unsaturated fat and not saturated fatty acid foods to avoid that increase in LDL-C.”
Generally, the evidence also shows that carbohydrate restriction typically leads to lower triglyceride levels and higher high-density lipoprotein (HDL) cholesterol levels. However, the same meta-analysis showed that the greatest reduction in LDL-C occurred at about 40% carbohydrate consumption.
Another recent meta-analysis showed that LDL-C rose significantly by an average 12.4 mg/dL with very-low-carb (3%-30%) diets, but only slightly, by 0.4 mg/dL, with moderate carb (40%-45%) intake.
Consuming very-low-carb diets did lead to greater reductions in triglycerides, compared with consuming moderate carb diets (23.9 mg/dL vs. 8.9 mg/dL).
“However, in terms of cardiovascular health, we are not entirely sure what that means. ... We have to look at the overall results in the presence of both triglyceride lowering as well as LDL cholesterol,” Dr. Kirkpatrick noted.
Carbohydrate restriction did consistently lead to lower hemoglobin A1c levels by an average of 0.4, 0.6, and 1.0 percentage points at 6 months for diets of 40%, 30%, and 15% carbohydrate, respectively. However, by 12 months, the effect had waned to 0.15, 0.2, and 0.4 A1c percentage points.
“Again, carbohydrate restriction, especially severe, is difficult for people to adhere to, and moderate carbohydrate intake would allow our patients to consume an appropriate amount of carbohydrate and still achieve improved glycemic control,” Dr. Kirkpatrick said.
Two large randomized controlled trials – PREDIMED and CORDIOPREV – examined the effects of the Mediterranean diet on cardiovascular disease prevention. Both showed a decrease in cardiovascular events with the Mediterranean diet, which involves consuming moderate amounts of carbohydrates.
“The Mediterranean dietary pattern has the strongest evidence for benefit, and it’s moderate in carbohydrates,” she concluded.
Very-low-carbohydrate eating is best
Dr. Griauzde was a last-minute replacement speaker for William S. Yancy Jr, MD, of Duke University, Durham, N.C., and presented his slides. She argued that consuming a very low carb diet improves glycemia and that it does not increase but possibly lowers cardiovascular risk.
She began by noting that prior to the discovery of insulin very-low-carb diets had been consumed for over a century to prolong life for people with type 1 diabetes.
“We have long recognized the deleterious role of carbohydrate in type 1 diabetes management, and we have increasingly recognized that role in the management of type 2 diabetes,” said Dr. Griauzde of the University of Michigan in Ann Arbor.
In a small study that compared maintaining a very-low-carb diet for 2 weeks with maintaining a high-carb diet for 2 weeks, total glucose areas under the curve were substantially lower (P < .05) during the low-carb phase, while A1c levels dropped from 7.3% to 6.8% (P = .006).
“We don’t see those outcomes with meds,” Dr. Griauzde noted, adding, “A diet very low in carbohydrates is one of the most potent tools we have to help our patients achieve glycemic control.”
Dr. Griauzde said that the carbohydrate-insulin model provides an explanation for why dietary carbohydrates are particularly obesogenic and metabolically harmful. That model contrasts with the energy balance model, which suggests that all calories are equal.
The rationale of the carbohydrate-insulin model is that dietary carbohydrate – either sugar or starch – raises serum glucose and insulin levels. A carbohydrate-restricted diet therefore reduces the dietary contribution to serum glucose, which then results in lower insulin levels. Insulin is a potent stimulator of lipogenesis (fat storage), and it is a potent inhibitor of lipolysis (the burning of fat). By lowering insulin levels, stored body fat is burned, serum ketone levels increase, and body weight is lowered.
This model suggests that, when insulin levels are chronically high because of excess carbohydrate consumption, circulating fuels are lowered, which leads to an increase in hunger and to overeating. This was demonstrated in a study that compared different levels of isocaloric glycemic index diets in 12 teenage boys with overweight or obesity. The higher-carbohydrate meals led to higher glucose and insulin levels and more food consumption.
In a systematic review of 13 trials of restricted-carbohydrate diets (< 45% carbohydrates) for adults with diabetes, the degree of improvement in A1c level correlated with the degree of carbohydrate restriction over 2-26 weeks (P = .013).
And in a network meta-analysis of 56 trials that compared nine diets among a total of 4,937 participants with type 2 diabetes, one conclusion was that “for reducing A1c, the low-carbohydrate diet was ranked as the best dietary approach (SUCRA: 84%), followed by the Mediterranean diet (80%), and Paleolithic diet (76%), compared with a control diet.”
Regarding the criticism that very-low-carbohydrate diets are high in saturated fat and therefore raise the risk of cardiovascular disease, Dr. Griauzde pointed to another meta-analysis of 21 prospective studies with more than 300,000 participants with 5-25 years of follow-up. In that analysis, the intake of saturated fat was not associated with an increased risk of cardiovascular disease or stroke.
Furthermore, a 12-week randomized controlled trial that involved 40 adults with overweight also suggested that a very-low-carb diet may be superior to a low-fat diet in improving aspects of the metabolic syndrome, including body mass index, lipid levels, and insulin sensitivity. Small LDL particles, which are more atherogenic than larger LDL particles, also decreased despite a threefold increase in saturated fat intake.
Rebuttals: Overall diet, patient preference matter
During the rebuttals, Dr. Kirkpatrick pointed out that large LDL particles are also atherogenic. In addition, she noted that the studies that showed that saturated fat isn’t associated with cardiovascular disease didn’t consider the macronutrients that replaced the saturated fat.
“It really is about increasing consumption of foods that we know are associated with cardiovascular benefit, including plant-based foods that are high quality and not refined carbohydrates ... and healthy protein sources. ... Hopefully we can step away from just looking at macronutrients and look at the total amount of food that people are choosing to eat.”
Importantly, Dr. Kirkpatrick said, patients need to be asked about their current dietary patterns and preferences. “Interventions should be patient centered and sensitive to cultural differences. Personalized lifestyle interventions increase the likelihood of success.”
Dr. Griauzde pointed out that newer antiobesity drugs can be added to any diet to decrease appetite and enhance adherence.
Dr. Griauzde also observed, “We can label a very-low-carbohydrate diet ‘extreme,’ but maybe, from the patient’s perspective, it’s extreme to take 200 units of insulin a day. If you can give them the opportunity to discontinue use of the insulin by following a very-low-carbohydrate dietary pattern, that is the opportunity that our patients deserve to have.”
But overall, she agreed with Dr. Kirkpatrick about individualizing any dietary approach: “We will never know from any of the trials that have been done or that will be done in the future what diet is best for an individual patient. ... Our job is to help our patients find the dietary approach that works best for them.”
Dr. Kirkpatrick is a clinical scientist with Midwest Biomedical Research, which has received funding from various food and pharmaceutical companies. She has not received any direct funding. Dr. Yancy is a consultant for The Simply Good Foods Co. Dr. Griauzde has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
It’s an ongoing debate in the diabetes world: Is it ideal to consume a very-low-carbohydrate diet, or is it better to go with moderate amounts of healthful carbs?
At the annual scientific sessions of the American Diabetes Association, Carol F. Kirkpatrick, PhD, RDN, spoke first, arguing in favor of diets consisting of moderate, high-quality carbohydrates.
Dina Hafez Griauzde, MD, countered that very-low-carbohydrate diets are more beneficial for people with diabetes, primarily type 2 diabetes.
Both speakers based their arguments on published evidence but agreed in the end that discussion with patients about individual dietary preferences should play a major role in the ultimate decision.
Moderate-carbohydrate eating is best
Dr. Kirkpatrick began by explaining that definitions of “low carb” vary in the literature, which makes comparisons between studies difficult. On the basis of a 2019 review that she coauthored, “moderate” carbohydrate consumption was defined as a diet in which 26%-44% of total daily calories are from carbohydrates. “Low” carbohydrate consumption was defined as a diet in which 10%-25% of calories were from carbohydrates. Consuming less than 10% was defined as a very-low-carbohydrate diet (i.e., a ketogenic diet).
Across studies, she noted, the literature shows that within the first 6 months weight loss is typically greater with carbohydrate-restricted diets than with higher-carbohydrate diets, but that by 1 year and beyond weight loss is similar.
“That can be partly due to the difficulty in people maintaining that very severe dietary restriction, although ... we can all acknowledge that it’s difficult for patients to adhere to any dietary pattern, so for sure by 12 months, the difference in the weight loss is gone between the two,” said Dr. Kirkpatrick, of Midwest Biomedical Research, Pocatello, Idaho.
In a recent meta-analysis of 35 trials that examined the dose-dependent effects of carbohydrate restriction for patients with type 2 diabetes, there was a significant decrease in weight as carbohydrates were reduced. But by 12 months (17 trials), the greatest weight reduction was seen at 35% carbohydrate intake.
“It may just be that people were able to adhere to that moderate intake better,” she explained.
Regarding lipids, in her 2019 review and in several meta-analyses since, the effects on low-density lipoprotein cholesterol (LDL-C) varied. For some patients, adhering to a low-carb diet led to reductions in LDL-C, especially if the participants also lost weight, whereas in other patients, a low-carb diet led to an increase in LDL-C.
Either way, a high intake of saturated fatty acids is key to an increase in LDL-C, Dr. Kirkpatrick noted. “So, it’s important that, if a patient chooses to follow a very low carbohydrate diet or any kind of dietary pattern that restricts carbohydrate, that they replace the carbohydrate with unsaturated fat and not saturated fatty acid foods to avoid that increase in LDL-C.”
Generally, the evidence also shows that carbohydrate restriction typically leads to lower triglyceride levels and higher high-density lipoprotein (HDL) cholesterol levels. However, the same meta-analysis showed that the greatest reduction in LDL-C occurred at about 40% carbohydrate consumption.
Another recent meta-analysis showed that LDL-C rose significantly by an average 12.4 mg/dL with very-low-carb (3%-30%) diets, but only slightly, by 0.4 mg/dL, with moderate carb (40%-45%) intake.
Consuming very-low-carb diets did lead to greater reductions in triglycerides, compared with consuming moderate carb diets (23.9 mg/dL vs. 8.9 mg/dL).
“However, in terms of cardiovascular health, we are not entirely sure what that means. ... We have to look at the overall results in the presence of both triglyceride lowering as well as LDL cholesterol,” Dr. Kirkpatrick noted.
Carbohydrate restriction did consistently lead to lower hemoglobin A1c levels by an average of 0.4, 0.6, and 1.0 percentage points at 6 months for diets of 40%, 30%, and 15% carbohydrate, respectively. However, by 12 months, the effect had waned to 0.15, 0.2, and 0.4 A1c percentage points.
“Again, carbohydrate restriction, especially severe, is difficult for people to adhere to, and moderate carbohydrate intake would allow our patients to consume an appropriate amount of carbohydrate and still achieve improved glycemic control,” Dr. Kirkpatrick said.
Two large randomized controlled trials – PREDIMED and CORDIOPREV – examined the effects of the Mediterranean diet on cardiovascular disease prevention. Both showed a decrease in cardiovascular events with the Mediterranean diet, which involves consuming moderate amounts of carbohydrates.
“The Mediterranean dietary pattern has the strongest evidence for benefit, and it’s moderate in carbohydrates,” she concluded.
Very-low-carbohydrate eating is best
Dr. Griauzde was a last-minute replacement speaker for William S. Yancy Jr, MD, of Duke University, Durham, N.C., and presented his slides. She argued that consuming a very low carb diet improves glycemia and that it does not increase but possibly lowers cardiovascular risk.
She began by noting that prior to the discovery of insulin very-low-carb diets had been consumed for over a century to prolong life for people with type 1 diabetes.
“We have long recognized the deleterious role of carbohydrate in type 1 diabetes management, and we have increasingly recognized that role in the management of type 2 diabetes,” said Dr. Griauzde of the University of Michigan in Ann Arbor.
In a small study that compared maintaining a very-low-carb diet for 2 weeks with maintaining a high-carb diet for 2 weeks, total glucose areas under the curve were substantially lower (P < .05) during the low-carb phase, while A1c levels dropped from 7.3% to 6.8% (P = .006).
“We don’t see those outcomes with meds,” Dr. Griauzde noted, adding, “A diet very low in carbohydrates is one of the most potent tools we have to help our patients achieve glycemic control.”
Dr. Griauzde said that the carbohydrate-insulin model provides an explanation for why dietary carbohydrates are particularly obesogenic and metabolically harmful. That model contrasts with the energy balance model, which suggests that all calories are equal.
The rationale of the carbohydrate-insulin model is that dietary carbohydrate – either sugar or starch – raises serum glucose and insulin levels. A carbohydrate-restricted diet therefore reduces the dietary contribution to serum glucose, which then results in lower insulin levels. Insulin is a potent stimulator of lipogenesis (fat storage), and it is a potent inhibitor of lipolysis (the burning of fat). By lowering insulin levels, stored body fat is burned, serum ketone levels increase, and body weight is lowered.
This model suggests that, when insulin levels are chronically high because of excess carbohydrate consumption, circulating fuels are lowered, which leads to an increase in hunger and to overeating. This was demonstrated in a study that compared different levels of isocaloric glycemic index diets in 12 teenage boys with overweight or obesity. The higher-carbohydrate meals led to higher glucose and insulin levels and more food consumption.
In a systematic review of 13 trials of restricted-carbohydrate diets (< 45% carbohydrates) for adults with diabetes, the degree of improvement in A1c level correlated with the degree of carbohydrate restriction over 2-26 weeks (P = .013).
And in a network meta-analysis of 56 trials that compared nine diets among a total of 4,937 participants with type 2 diabetes, one conclusion was that “for reducing A1c, the low-carbohydrate diet was ranked as the best dietary approach (SUCRA: 84%), followed by the Mediterranean diet (80%), and Paleolithic diet (76%), compared with a control diet.”
Regarding the criticism that very-low-carbohydrate diets are high in saturated fat and therefore raise the risk of cardiovascular disease, Dr. Griauzde pointed to another meta-analysis of 21 prospective studies with more than 300,000 participants with 5-25 years of follow-up. In that analysis, the intake of saturated fat was not associated with an increased risk of cardiovascular disease or stroke.
Furthermore, a 12-week randomized controlled trial that involved 40 adults with overweight also suggested that a very-low-carb diet may be superior to a low-fat diet in improving aspects of the metabolic syndrome, including body mass index, lipid levels, and insulin sensitivity. Small LDL particles, which are more atherogenic than larger LDL particles, also decreased despite a threefold increase in saturated fat intake.
Rebuttals: Overall diet, patient preference matter
During the rebuttals, Dr. Kirkpatrick pointed out that large LDL particles are also atherogenic. In addition, she noted that the studies that showed that saturated fat isn’t associated with cardiovascular disease didn’t consider the macronutrients that replaced the saturated fat.
“It really is about increasing consumption of foods that we know are associated with cardiovascular benefit, including plant-based foods that are high quality and not refined carbohydrates ... and healthy protein sources. ... Hopefully we can step away from just looking at macronutrients and look at the total amount of food that people are choosing to eat.”
Importantly, Dr. Kirkpatrick said, patients need to be asked about their current dietary patterns and preferences. “Interventions should be patient centered and sensitive to cultural differences. Personalized lifestyle interventions increase the likelihood of success.”
Dr. Griauzde pointed out that newer antiobesity drugs can be added to any diet to decrease appetite and enhance adherence.
Dr. Griauzde also observed, “We can label a very-low-carbohydrate diet ‘extreme,’ but maybe, from the patient’s perspective, it’s extreme to take 200 units of insulin a day. If you can give them the opportunity to discontinue use of the insulin by following a very-low-carbohydrate dietary pattern, that is the opportunity that our patients deserve to have.”
But overall, she agreed with Dr. Kirkpatrick about individualizing any dietary approach: “We will never know from any of the trials that have been done or that will be done in the future what diet is best for an individual patient. ... Our job is to help our patients find the dietary approach that works best for them.”
Dr. Kirkpatrick is a clinical scientist with Midwest Biomedical Research, which has received funding from various food and pharmaceutical companies. She has not received any direct funding. Dr. Yancy is a consultant for The Simply Good Foods Co. Dr. Griauzde has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ADA 2023
Morning vs. afternoon exercise debate: A false dichotomy
Should we be exercising in the morning or afternoon? Before a meal or after a meal?
Popular media outlets, researchers, and clinicians seem to love these debates. I hate them. For me, it’s a false dichotomy. A false dichotomy is when people argue two sides as if only one option exists. A winner must be crowned, and a loser exists. But
Some but not all research suggests that morning fasted exercise may be the best time of day and condition to work out for weight control and training adaptations. Morning exercise may be a bit better for logistical reasons if you like to get up early. Some of us are indeed early chronotypes who rise early, get as much done as we can, including all our fitness and work-related activities, and then head to bed early (for me that is about 10 PM). Getting an early morning workout seems to fit with our schedules as morning larks.
But if you are a late-day chronotype, early exercise may not be in sync with your low morning energy levels or your preference for leisure-time activities later in the day. And lots of people with diabetes prefer to eat and then exercise. Late chronotypes are less physically active in general, compared with early chronotypes, and those who train in the morning tend to have better training adherence and expend more energy overall throughout the day. According to Dr. Normand Boulé from the University of Alberta, Edmonton, who presented on the topic of exercise time of day at the recent scientific sessions of the American Diabetes Association in San Diego, morning exercise in the fasted state tends to be associated with higher rates of fat oxidation, better weight control, and better skeletal muscle adaptations over time, compared with exercise performed later in the day. Dr Boulé also proposed that fasted exercise might be superior for training adaptations and long-term glycemia if you have type 2 diabetes.
But the argument for morning-only exercise falls short when we look specifically at postmeal glycemia, according to Dr. Jenna Gillen from the University of Toronto, who faced off against Dr. Boulé at a debate at the meeting and also publishes on the topic. She pointed out that mild to moderate intensity exercising done soon after meals typically results in fewer glucose spikes after meals in people with diabetes, and her argument is supported by at least one recent meta-analysis where postmeal walking was best for improving glycemia in those with prediabetes and type 2 diabetes.
The notion that postmeal or afternoon exercise is best for people with type 2 diabetes is also supported by a recent reexamination of the original Look AHEAD Trial of over 2,400 adults with type 2 diabetes, wherein the role of lifestyle intervention on cardiovascular outcomes was the original goal. In this recent secondary analysis of the Look AHEAD Trial, those most active in the afternoon (between 1:43 p.m. and 5:00 p.m.) had the greatest improvements in their overall glucose control after 1 year of the intensive lifestyle intervention, compared with exercise at other times of day. Afternoon exercisers were also more likely to have complete “remission” of their diabetes, as defined by no longer needing any glucose-lowering agents to control their glucose levels. But this was not a study that was designed for determining whether exercise time of day matters for glycemia because the participants were not randomly assigned to a set time of day for their activity, and glycemic control was not the primary endpoint (cardiovascular events were).
But hold on a minute. I said this was a false-dichotomy argument. It is. Just because it may or may not be “better” for your glucose to exercise in the morning vs. afternoon, if you have diabetes, it doesn’t mean you have to choose one or the other. You could choose neither (okay, that’s bad), both, or you could alternate between the two. For me this argument is like saying; “There only one time of day to save money”; “to tell a joke”; “to eat a meal” (okay, that’s another useless debate); or “do my laundry” (my mother once told me it’s technically cheaper after 6 p.m.!).
I live with diabetes, and I take insulin. I like how morning exercise in the form of a run with my dog wakes me up, sets me up for the day with positive thoughts, helps generate lots of creative ideas, and perhaps more importantly for me, it tends not to result in hypoglycemia because my insulin on board is lowest then.
Exercise later in the day is tricky when taking insulin because it tends to result in a higher insulin “potency effect” with prandial insulins. However, I still like midday activity and late-day exercise. For example, taking an activity break after lunch blunts the rise in my glucose and breaks up my prolonged sitting time in the office. After-dinner exercise allows me to spend a little more time with my wife, dog, or friends outdoors as the hot summer day begins to cool off. On Monday nights, I play basketball because that’s the only time we can book the gymnasium and that may not end until 9:45 p.m. (15 minutes before I want to go to bed; if you remember, I am a lark). That can result in two frustrating things related to my diabetes: It can cause an immediate rise in my glucose because of a competitive stress response and then a drop in my glucose overnight when I’m sleeping. But I still do it. I know that the training I’m doing at any point of the day will benefit me in lots of little ways, and I think we all need to take as many opportunities to be physically active as we possibly can. My kids and I coin this our daily “fitness opportunities,” and it does not matter to me if its morning, noon, or night!
It’s time to make the headlines and arguments stop. There is no wrong time of day to exercise. At least not in my opinion.
Dr. Riddle is a full professor in the school of kinesiology and health science at York University and senior scientist at LMC Diabetes & Endocrinology, both in Toronto. He has disclosed financial relationships with Dexcom, Eli Lilly, Indigo Diabetes, Insulet, Novo Nordisk, Sanofi, Supersapiens, and Zucara Therapeutics.
A version of this article first appeared on Medscape.com.
Should we be exercising in the morning or afternoon? Before a meal or after a meal?
Popular media outlets, researchers, and clinicians seem to love these debates. I hate them. For me, it’s a false dichotomy. A false dichotomy is when people argue two sides as if only one option exists. A winner must be crowned, and a loser exists. But
Some but not all research suggests that morning fasted exercise may be the best time of day and condition to work out for weight control and training adaptations. Morning exercise may be a bit better for logistical reasons if you like to get up early. Some of us are indeed early chronotypes who rise early, get as much done as we can, including all our fitness and work-related activities, and then head to bed early (for me that is about 10 PM). Getting an early morning workout seems to fit with our schedules as morning larks.
But if you are a late-day chronotype, early exercise may not be in sync with your low morning energy levels or your preference for leisure-time activities later in the day. And lots of people with diabetes prefer to eat and then exercise. Late chronotypes are less physically active in general, compared with early chronotypes, and those who train in the morning tend to have better training adherence and expend more energy overall throughout the day. According to Dr. Normand Boulé from the University of Alberta, Edmonton, who presented on the topic of exercise time of day at the recent scientific sessions of the American Diabetes Association in San Diego, morning exercise in the fasted state tends to be associated with higher rates of fat oxidation, better weight control, and better skeletal muscle adaptations over time, compared with exercise performed later in the day. Dr Boulé also proposed that fasted exercise might be superior for training adaptations and long-term glycemia if you have type 2 diabetes.
But the argument for morning-only exercise falls short when we look specifically at postmeal glycemia, according to Dr. Jenna Gillen from the University of Toronto, who faced off against Dr. Boulé at a debate at the meeting and also publishes on the topic. She pointed out that mild to moderate intensity exercising done soon after meals typically results in fewer glucose spikes after meals in people with diabetes, and her argument is supported by at least one recent meta-analysis where postmeal walking was best for improving glycemia in those with prediabetes and type 2 diabetes.
The notion that postmeal or afternoon exercise is best for people with type 2 diabetes is also supported by a recent reexamination of the original Look AHEAD Trial of over 2,400 adults with type 2 diabetes, wherein the role of lifestyle intervention on cardiovascular outcomes was the original goal. In this recent secondary analysis of the Look AHEAD Trial, those most active in the afternoon (between 1:43 p.m. and 5:00 p.m.) had the greatest improvements in their overall glucose control after 1 year of the intensive lifestyle intervention, compared with exercise at other times of day. Afternoon exercisers were also more likely to have complete “remission” of their diabetes, as defined by no longer needing any glucose-lowering agents to control their glucose levels. But this was not a study that was designed for determining whether exercise time of day matters for glycemia because the participants were not randomly assigned to a set time of day for their activity, and glycemic control was not the primary endpoint (cardiovascular events were).
But hold on a minute. I said this was a false-dichotomy argument. It is. Just because it may or may not be “better” for your glucose to exercise in the morning vs. afternoon, if you have diabetes, it doesn’t mean you have to choose one or the other. You could choose neither (okay, that’s bad), both, or you could alternate between the two. For me this argument is like saying; “There only one time of day to save money”; “to tell a joke”; “to eat a meal” (okay, that’s another useless debate); or “do my laundry” (my mother once told me it’s technically cheaper after 6 p.m.!).
I live with diabetes, and I take insulin. I like how morning exercise in the form of a run with my dog wakes me up, sets me up for the day with positive thoughts, helps generate lots of creative ideas, and perhaps more importantly for me, it tends not to result in hypoglycemia because my insulin on board is lowest then.
Exercise later in the day is tricky when taking insulin because it tends to result in a higher insulin “potency effect” with prandial insulins. However, I still like midday activity and late-day exercise. For example, taking an activity break after lunch blunts the rise in my glucose and breaks up my prolonged sitting time in the office. After-dinner exercise allows me to spend a little more time with my wife, dog, or friends outdoors as the hot summer day begins to cool off. On Monday nights, I play basketball because that’s the only time we can book the gymnasium and that may not end until 9:45 p.m. (15 minutes before I want to go to bed; if you remember, I am a lark). That can result in two frustrating things related to my diabetes: It can cause an immediate rise in my glucose because of a competitive stress response and then a drop in my glucose overnight when I’m sleeping. But I still do it. I know that the training I’m doing at any point of the day will benefit me in lots of little ways, and I think we all need to take as many opportunities to be physically active as we possibly can. My kids and I coin this our daily “fitness opportunities,” and it does not matter to me if its morning, noon, or night!
It’s time to make the headlines and arguments stop. There is no wrong time of day to exercise. At least not in my opinion.
Dr. Riddle is a full professor in the school of kinesiology and health science at York University and senior scientist at LMC Diabetes & Endocrinology, both in Toronto. He has disclosed financial relationships with Dexcom, Eli Lilly, Indigo Diabetes, Insulet, Novo Nordisk, Sanofi, Supersapiens, and Zucara Therapeutics.
A version of this article first appeared on Medscape.com.
Should we be exercising in the morning or afternoon? Before a meal or after a meal?
Popular media outlets, researchers, and clinicians seem to love these debates. I hate them. For me, it’s a false dichotomy. A false dichotomy is when people argue two sides as if only one option exists. A winner must be crowned, and a loser exists. But
Some but not all research suggests that morning fasted exercise may be the best time of day and condition to work out for weight control and training adaptations. Morning exercise may be a bit better for logistical reasons if you like to get up early. Some of us are indeed early chronotypes who rise early, get as much done as we can, including all our fitness and work-related activities, and then head to bed early (for me that is about 10 PM). Getting an early morning workout seems to fit with our schedules as morning larks.
But if you are a late-day chronotype, early exercise may not be in sync with your low morning energy levels or your preference for leisure-time activities later in the day. And lots of people with diabetes prefer to eat and then exercise. Late chronotypes are less physically active in general, compared with early chronotypes, and those who train in the morning tend to have better training adherence and expend more energy overall throughout the day. According to Dr. Normand Boulé from the University of Alberta, Edmonton, who presented on the topic of exercise time of day at the recent scientific sessions of the American Diabetes Association in San Diego, morning exercise in the fasted state tends to be associated with higher rates of fat oxidation, better weight control, and better skeletal muscle adaptations over time, compared with exercise performed later in the day. Dr Boulé also proposed that fasted exercise might be superior for training adaptations and long-term glycemia if you have type 2 diabetes.
But the argument for morning-only exercise falls short when we look specifically at postmeal glycemia, according to Dr. Jenna Gillen from the University of Toronto, who faced off against Dr. Boulé at a debate at the meeting and also publishes on the topic. She pointed out that mild to moderate intensity exercising done soon after meals typically results in fewer glucose spikes after meals in people with diabetes, and her argument is supported by at least one recent meta-analysis where postmeal walking was best for improving glycemia in those with prediabetes and type 2 diabetes.
The notion that postmeal or afternoon exercise is best for people with type 2 diabetes is also supported by a recent reexamination of the original Look AHEAD Trial of over 2,400 adults with type 2 diabetes, wherein the role of lifestyle intervention on cardiovascular outcomes was the original goal. In this recent secondary analysis of the Look AHEAD Trial, those most active in the afternoon (between 1:43 p.m. and 5:00 p.m.) had the greatest improvements in their overall glucose control after 1 year of the intensive lifestyle intervention, compared with exercise at other times of day. Afternoon exercisers were also more likely to have complete “remission” of their diabetes, as defined by no longer needing any glucose-lowering agents to control their glucose levels. But this was not a study that was designed for determining whether exercise time of day matters for glycemia because the participants were not randomly assigned to a set time of day for their activity, and glycemic control was not the primary endpoint (cardiovascular events were).
But hold on a minute. I said this was a false-dichotomy argument. It is. Just because it may or may not be “better” for your glucose to exercise in the morning vs. afternoon, if you have diabetes, it doesn’t mean you have to choose one or the other. You could choose neither (okay, that’s bad), both, or you could alternate between the two. For me this argument is like saying; “There only one time of day to save money”; “to tell a joke”; “to eat a meal” (okay, that’s another useless debate); or “do my laundry” (my mother once told me it’s technically cheaper after 6 p.m.!).
I live with diabetes, and I take insulin. I like how morning exercise in the form of a run with my dog wakes me up, sets me up for the day with positive thoughts, helps generate lots of creative ideas, and perhaps more importantly for me, it tends not to result in hypoglycemia because my insulin on board is lowest then.
Exercise later in the day is tricky when taking insulin because it tends to result in a higher insulin “potency effect” with prandial insulins. However, I still like midday activity and late-day exercise. For example, taking an activity break after lunch blunts the rise in my glucose and breaks up my prolonged sitting time in the office. After-dinner exercise allows me to spend a little more time with my wife, dog, or friends outdoors as the hot summer day begins to cool off. On Monday nights, I play basketball because that’s the only time we can book the gymnasium and that may not end until 9:45 p.m. (15 minutes before I want to go to bed; if you remember, I am a lark). That can result in two frustrating things related to my diabetes: It can cause an immediate rise in my glucose because of a competitive stress response and then a drop in my glucose overnight when I’m sleeping. But I still do it. I know that the training I’m doing at any point of the day will benefit me in lots of little ways, and I think we all need to take as many opportunities to be physically active as we possibly can. My kids and I coin this our daily “fitness opportunities,” and it does not matter to me if its morning, noon, or night!
It’s time to make the headlines and arguments stop. There is no wrong time of day to exercise. At least not in my opinion.
Dr. Riddle is a full professor in the school of kinesiology and health science at York University and senior scientist at LMC Diabetes & Endocrinology, both in Toronto. He has disclosed financial relationships with Dexcom, Eli Lilly, Indigo Diabetes, Insulet, Novo Nordisk, Sanofi, Supersapiens, and Zucara Therapeutics.
A version of this article first appeared on Medscape.com.
Growth hormone links with worse T2D control in adolescents
SAN DIEGO – Plasma levels of three proteins involved in growth hormone activity showed significant links to the controllability of type 2 diabetes in children, a finding that suggests these proteins may serve as risk markers for incident type 2 diabetes and help identify adolescents who could benefit from aggressive preventive care.
“Plasma growth hormone mediators are associated with glycemic failure in youth with type 2 diabetes,” Chang Lu, MD, said at the at the annual scientific sessions of the American Diabetes Association. “Our hope is that these mediators could be biomarkers for predicting type 2 diabetes onset,” she added in an interview.
Another potential application is to “leverage these data to find predictive markers” that could identify adolescents with type 2 diabetes “at risk for particularly aggressive disease and target them for more intervention,” added Elvira M. Isganaitis, MD, senior author of the report and a pediatric endocrinologist at the Joslin Diabetes Center in Boston.
Does growth hormone cause incident T2D at puberty?
Changes in levels of growth hormone–associated peptides during puberty “could potentially explain why children with type 2 diabetes have a more aggressive course” of the disorder, added Dr. Lu, a pediatric endocrinologist at Joslin and at Boston’s Children’s Hospital.
Puberty-associated changes in growth hormone and related peptides “could be why type 2 diabetes starts during puberty. Type 2 diabetes is almost unheard of before children reach about age 10,” Dr. Isganaitis said in an interview.
A current hypothesis is that “high levels of growth hormone is a cause of insulin resistance during puberty, but in healthy children their beta cells overcome this by making more insulin and so they do not develop diabetes,” said Kristen J. Nadeau, MD, a pediatric endocrinologist and professor at Children’s Hospital Colorado in Denver.
“But this is a stress situation, and if someone has poor beta-cell function they may develop diabetes. The increase in growth hormone [during puberty] can unmask a physiologic and genetic predisposition” to developing type 2 diabetes, Dr. Nadeau said in an interview.
The analyses run by Dr. Lu, Dr. Isganaitis, and their coauthors used data collected in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, which randomized 699 children aged 10-17 years with type 2 diabetes to one of three antidiabetes treatment regimens and tallied the subsequent incidence of glycemic failure. The study defined the latter as either 6 months with a hemoglobin A1c level of at least 8% or need for insulin treatment.
The primary outcome showed a 39%-52% incidence of failure during 5 years of follow-up depending on the specific treatments the study participants received.
Growth hormone correlates of glycemic failure
The new analyses focused on 310 study participants from TODAY who had plasma specimens available from baseline and a second specimen obtained after 3 years of follow-up. The researchers compared the levels of three peptides that mediate growth hormone signaling at baseline and after 3 years, and assessed these changes relative to the endpoint of glycemic failure.
The results showed that an increase in insulin-like growth factor-1 significantly linked with a reduced incidence of glycemic failure and improved glycemia and beta-cell function.
In contrast, Also, an increase in insulin-like growth factor binding protein-1 significantly linked with glycemic failure and hyperglycemia at 36 months, and with higher insulin sensitivity at baseline. All these analyses adjusted for baseline differences in several demographic and clinical variables.
But these post hoc analyses could not determine whether these associations resulted from, or had a causal role in, treatment failure, cautioned Dr. Lu.
Future studies should examine the relationship of growth hormone signaling and the course of glycemic control in children and adolescents with prediabetes and obesity, Dr. Lu said.
Confirming that these growth hormone-related proteins are reliable predictors of future glycemic dysfunction would open the door to studies of interventions to slow or prevent progression to type 2 diabetes in children identified as high risk.
Potential interventions include early initiation of insulin treatment, which could help preserve beta-cell function, or treatment with a glucagon-like peptide-1 (GLP-1) agonist, a class of agents that may interact with the insulin-like growth factor-1 receptors on beta cells, Dr. Lu said.
The study received no commercial funding. Dr. Lu, Dr. Isganaitis, and Dr. Nadeau reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
SAN DIEGO – Plasma levels of three proteins involved in growth hormone activity showed significant links to the controllability of type 2 diabetes in children, a finding that suggests these proteins may serve as risk markers for incident type 2 diabetes and help identify adolescents who could benefit from aggressive preventive care.
“Plasma growth hormone mediators are associated with glycemic failure in youth with type 2 diabetes,” Chang Lu, MD, said at the at the annual scientific sessions of the American Diabetes Association. “Our hope is that these mediators could be biomarkers for predicting type 2 diabetes onset,” she added in an interview.
Another potential application is to “leverage these data to find predictive markers” that could identify adolescents with type 2 diabetes “at risk for particularly aggressive disease and target them for more intervention,” added Elvira M. Isganaitis, MD, senior author of the report and a pediatric endocrinologist at the Joslin Diabetes Center in Boston.
Does growth hormone cause incident T2D at puberty?
Changes in levels of growth hormone–associated peptides during puberty “could potentially explain why children with type 2 diabetes have a more aggressive course” of the disorder, added Dr. Lu, a pediatric endocrinologist at Joslin and at Boston’s Children’s Hospital.
Puberty-associated changes in growth hormone and related peptides “could be why type 2 diabetes starts during puberty. Type 2 diabetes is almost unheard of before children reach about age 10,” Dr. Isganaitis said in an interview.
A current hypothesis is that “high levels of growth hormone is a cause of insulin resistance during puberty, but in healthy children their beta cells overcome this by making more insulin and so they do not develop diabetes,” said Kristen J. Nadeau, MD, a pediatric endocrinologist and professor at Children’s Hospital Colorado in Denver.
“But this is a stress situation, and if someone has poor beta-cell function they may develop diabetes. The increase in growth hormone [during puberty] can unmask a physiologic and genetic predisposition” to developing type 2 diabetes, Dr. Nadeau said in an interview.
The analyses run by Dr. Lu, Dr. Isganaitis, and their coauthors used data collected in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, which randomized 699 children aged 10-17 years with type 2 diabetes to one of three antidiabetes treatment regimens and tallied the subsequent incidence of glycemic failure. The study defined the latter as either 6 months with a hemoglobin A1c level of at least 8% or need for insulin treatment.
The primary outcome showed a 39%-52% incidence of failure during 5 years of follow-up depending on the specific treatments the study participants received.
Growth hormone correlates of glycemic failure
The new analyses focused on 310 study participants from TODAY who had plasma specimens available from baseline and a second specimen obtained after 3 years of follow-up. The researchers compared the levels of three peptides that mediate growth hormone signaling at baseline and after 3 years, and assessed these changes relative to the endpoint of glycemic failure.
The results showed that an increase in insulin-like growth factor-1 significantly linked with a reduced incidence of glycemic failure and improved glycemia and beta-cell function.
In contrast, Also, an increase in insulin-like growth factor binding protein-1 significantly linked with glycemic failure and hyperglycemia at 36 months, and with higher insulin sensitivity at baseline. All these analyses adjusted for baseline differences in several demographic and clinical variables.
But these post hoc analyses could not determine whether these associations resulted from, or had a causal role in, treatment failure, cautioned Dr. Lu.
Future studies should examine the relationship of growth hormone signaling and the course of glycemic control in children and adolescents with prediabetes and obesity, Dr. Lu said.
Confirming that these growth hormone-related proteins are reliable predictors of future glycemic dysfunction would open the door to studies of interventions to slow or prevent progression to type 2 diabetes in children identified as high risk.
Potential interventions include early initiation of insulin treatment, which could help preserve beta-cell function, or treatment with a glucagon-like peptide-1 (GLP-1) agonist, a class of agents that may interact with the insulin-like growth factor-1 receptors on beta cells, Dr. Lu said.
The study received no commercial funding. Dr. Lu, Dr. Isganaitis, and Dr. Nadeau reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
SAN DIEGO – Plasma levels of three proteins involved in growth hormone activity showed significant links to the controllability of type 2 diabetes in children, a finding that suggests these proteins may serve as risk markers for incident type 2 diabetes and help identify adolescents who could benefit from aggressive preventive care.
“Plasma growth hormone mediators are associated with glycemic failure in youth with type 2 diabetes,” Chang Lu, MD, said at the at the annual scientific sessions of the American Diabetes Association. “Our hope is that these mediators could be biomarkers for predicting type 2 diabetes onset,” she added in an interview.
Another potential application is to “leverage these data to find predictive markers” that could identify adolescents with type 2 diabetes “at risk for particularly aggressive disease and target them for more intervention,” added Elvira M. Isganaitis, MD, senior author of the report and a pediatric endocrinologist at the Joslin Diabetes Center in Boston.
Does growth hormone cause incident T2D at puberty?
Changes in levels of growth hormone–associated peptides during puberty “could potentially explain why children with type 2 diabetes have a more aggressive course” of the disorder, added Dr. Lu, a pediatric endocrinologist at Joslin and at Boston’s Children’s Hospital.
Puberty-associated changes in growth hormone and related peptides “could be why type 2 diabetes starts during puberty. Type 2 diabetes is almost unheard of before children reach about age 10,” Dr. Isganaitis said in an interview.
A current hypothesis is that “high levels of growth hormone is a cause of insulin resistance during puberty, but in healthy children their beta cells overcome this by making more insulin and so they do not develop diabetes,” said Kristen J. Nadeau, MD, a pediatric endocrinologist and professor at Children’s Hospital Colorado in Denver.
“But this is a stress situation, and if someone has poor beta-cell function they may develop diabetes. The increase in growth hormone [during puberty] can unmask a physiologic and genetic predisposition” to developing type 2 diabetes, Dr. Nadeau said in an interview.
The analyses run by Dr. Lu, Dr. Isganaitis, and their coauthors used data collected in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, which randomized 699 children aged 10-17 years with type 2 diabetes to one of three antidiabetes treatment regimens and tallied the subsequent incidence of glycemic failure. The study defined the latter as either 6 months with a hemoglobin A1c level of at least 8% or need for insulin treatment.
The primary outcome showed a 39%-52% incidence of failure during 5 years of follow-up depending on the specific treatments the study participants received.
Growth hormone correlates of glycemic failure
The new analyses focused on 310 study participants from TODAY who had plasma specimens available from baseline and a second specimen obtained after 3 years of follow-up. The researchers compared the levels of three peptides that mediate growth hormone signaling at baseline and after 3 years, and assessed these changes relative to the endpoint of glycemic failure.
The results showed that an increase in insulin-like growth factor-1 significantly linked with a reduced incidence of glycemic failure and improved glycemia and beta-cell function.
In contrast, Also, an increase in insulin-like growth factor binding protein-1 significantly linked with glycemic failure and hyperglycemia at 36 months, and with higher insulin sensitivity at baseline. All these analyses adjusted for baseline differences in several demographic and clinical variables.
But these post hoc analyses could not determine whether these associations resulted from, or had a causal role in, treatment failure, cautioned Dr. Lu.
Future studies should examine the relationship of growth hormone signaling and the course of glycemic control in children and adolescents with prediabetes and obesity, Dr. Lu said.
Confirming that these growth hormone-related proteins are reliable predictors of future glycemic dysfunction would open the door to studies of interventions to slow or prevent progression to type 2 diabetes in children identified as high risk.
Potential interventions include early initiation of insulin treatment, which could help preserve beta-cell function, or treatment with a glucagon-like peptide-1 (GLP-1) agonist, a class of agents that may interact with the insulin-like growth factor-1 receptors on beta cells, Dr. Lu said.
The study received no commercial funding. Dr. Lu, Dr. Isganaitis, and Dr. Nadeau reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
AT ADA 2023
Benefits of bariatric surgery persist for 12 years
SAN DIEGO – and a baseline body mass index (BMI) of at least 27 kg/m2, according to new study results.
The findings are from ARMMS-T2D, a prospective, controlled trial with the largest cohort and longest follow-up of bariatric surgery reported to date. The results reinforce the potential role of surgery “as an option to improve diabetes-related outcomes, including people with a BMI of less than 35 kg/m2,” said Anita P. Courcoulas, MD, at the recent annual scientific sessions of the American Diabetes Association.
People who underwent bariatric surgery (gastric band, sleeve gastrectomy, or Roux-en-Y gastric bypass) had an average 1.6–percentage point drop in hemoglobin A1c from baseline 7 years after surgery and an average 1.4–percentage point reduction from baseline after 12 years. Average decreases from baseline were 0.2 and 0.3 percentage points at these time points, respectively, among controls who underwent lifestyle and medical interventions only. Between-group differences were significant at both the 7-year (primary endpoint) and 12-year time points in the intention-to-treat analysis, reported Dr. Courcoulas, a professor of surgery at the University of Pittsburgh.
Average weight loss from baseline to 7 and 12 years was 19.9% and 19.3%, respectively, in the surgery group and 8.3% and 10.8%, respectively, among controls, which was significantly different between groups at both time points (a secondary endpoint).
Dr. Courcoulas highlighted that the 10.8% average weight loss after 12 years among controls included crossovers, with 25% of patients progressing from their initial intervention of lifestyle and medical management to undergoing bariatric surgery during follow-up. Among the controls who never underwent surgery (per-protocol analysis), the 12-year average weight loss from baseline was 7.3%.
High-dose incretin-hormone therapy missing
A major limitation of ARMMS-T2D (Alliance of Randomized Trials of Medicine vs. Metabolic Surgery in Type 2 Diabetes) is that it prospectively followed a combined cohort from four independently run controlled U.S. trials that all began more than a decade ago, before the contemporary era of medical weight loss management that’s been revolutionized by incretin-hormone receptor agonists such as semaglutide (Ozempic/Wegovy, Novo Nordisk) and tirzepatide (Mounjaro, Lilly).
New randomized, controlled trials “are needed” that compare metabolic bariatric surgery with medical and lifestyle management that includes “high-dose incretin-hormone therapy,” commented Robert H. Eckel, MD, designated discussant for ARMMS-T2D at the session.
The results also showed notable rates of two adverse events associated with bariatric surgery: a 14% incidence of bone fractures, compared with a rate of 5% among controls, and a 12% incidence of anemia after surgery, compared with a rate of 3% among controls.
The control group also had a significantly higher 3% incidence of new need for hemodialysis, compared with no incident dialysis cases among the surgery patients.
“The fracture difference [after bariatric surgery] needs more careful follow-up,” commented Dr. Eckel, an endocrinologist and emeritus professor at the University of Colorado at Denver, Aurora.
ARMMS-T2D included data from 262 people with overweight or obesity and type 2 diabetes randomized in any of four U.S. studies that compared the outcomes of 166 patients who underwent bariatric surgery with 96 patients who served as controls and had lifestyle and medical interventions for weight loss and glycemic control. Seven-year follow-up included 82 (85%) of the initial 96 control patients and 136 (82%) of the initial 166 surgery patients. After 12 years, 31 of the controls (32%) and 83 surgery patients (50%) remained for the A1c analysis.
A quartet of studies joined together
The ARMMS-T2D prospective analysis resulted from an early partnership by the organizers of the four independent randomized studies that compared bariatric surgery with lifestyle and medical intervention in people with type 2 diabetes and overweight or obesity: STAMPEDE, which included 150 people at the Cleveland Clinic starting in 2007; SLIMM-T2D, which included 88 people at Brigham and Women’s Hospital and the Joslin Diabetes Center in Boston starting in 2010; TRIABETES, which included 69 people at the University of Pittsburgh starting in 2009; and CROSSROADS, which included 43 people at the University of Washington, Seattle, starting in 2011.
Further secondary findings from the ARMMS-T2D analyses showed that 38% of the surgery patients and 17% of controls had an A1c < 6.5% after 7 years.
At 7 years, type 2 diabetes remission, defined as those with an A1c < 6.5% who were not taking any antidiabetes medications, was reached in 18% of surgery patients and 6% of controls. At 12 years, 13% of the surgery patients and none of the controls met this metric, Dr. Courcoulas said.
The duration of diabetes a person had before undergoing bariatric surgery “may be an important factor” as to whether patients undergo remission, suggested Dr. Eckel. He noted that longer duration type 2 diabetes usually results in increased glucose intolerance and makes remission less likely
Roux-en-Y gastric bypass appeared to have the best rates of patients achieving both lower A1c levels and more weight loss, followed by sleeve gastrectomy and gastric banding, which had the worst performance. But Dr. Courcoulas cautioned that the study was underpowered to reliably compare individual surgical procedures.
In terms of those with an A1c < 7.0%, surgery patients maintained a steady prevalence rate of about 55% during the first 5 years of follow-up, roughly twice the rate of controls, at 28% during all years of follow-up starting at year 5.
About 37% of enrolled patients had a BMI < 35 kg/m2, and the A1c-lowering benefit and weight loss in this subgroup were consistent with the overall findings, which supports consideration of bariatric surgery for people with type 2 diabetes and a BMI < 35 kg/m2, Dr. Courcoulas said.
She also highlighted that bariatric surgery was linked with significant reductions in triglyceride levels and increased high-density lipoprotein cholesterol levels, compared with controls. However, 22% of surgery patients experienced abdominal pain, compared with 10% of controls, and 7% experienced dysphagia, compared with no cases among the controls.
ARMMS-T2D received no commercial funding. Dr. Courcoulas had no disclosures. Dr. Eckel has been a consultant to numerous companies but said he had no relevant disclosures.
A version of this article first appeared on Medscape.com.
SAN DIEGO – and a baseline body mass index (BMI) of at least 27 kg/m2, according to new study results.
The findings are from ARMMS-T2D, a prospective, controlled trial with the largest cohort and longest follow-up of bariatric surgery reported to date. The results reinforce the potential role of surgery “as an option to improve diabetes-related outcomes, including people with a BMI of less than 35 kg/m2,” said Anita P. Courcoulas, MD, at the recent annual scientific sessions of the American Diabetes Association.
People who underwent bariatric surgery (gastric band, sleeve gastrectomy, or Roux-en-Y gastric bypass) had an average 1.6–percentage point drop in hemoglobin A1c from baseline 7 years after surgery and an average 1.4–percentage point reduction from baseline after 12 years. Average decreases from baseline were 0.2 and 0.3 percentage points at these time points, respectively, among controls who underwent lifestyle and medical interventions only. Between-group differences were significant at both the 7-year (primary endpoint) and 12-year time points in the intention-to-treat analysis, reported Dr. Courcoulas, a professor of surgery at the University of Pittsburgh.
Average weight loss from baseline to 7 and 12 years was 19.9% and 19.3%, respectively, in the surgery group and 8.3% and 10.8%, respectively, among controls, which was significantly different between groups at both time points (a secondary endpoint).
Dr. Courcoulas highlighted that the 10.8% average weight loss after 12 years among controls included crossovers, with 25% of patients progressing from their initial intervention of lifestyle and medical management to undergoing bariatric surgery during follow-up. Among the controls who never underwent surgery (per-protocol analysis), the 12-year average weight loss from baseline was 7.3%.
High-dose incretin-hormone therapy missing
A major limitation of ARMMS-T2D (Alliance of Randomized Trials of Medicine vs. Metabolic Surgery in Type 2 Diabetes) is that it prospectively followed a combined cohort from four independently run controlled U.S. trials that all began more than a decade ago, before the contemporary era of medical weight loss management that’s been revolutionized by incretin-hormone receptor agonists such as semaglutide (Ozempic/Wegovy, Novo Nordisk) and tirzepatide (Mounjaro, Lilly).
New randomized, controlled trials “are needed” that compare metabolic bariatric surgery with medical and lifestyle management that includes “high-dose incretin-hormone therapy,” commented Robert H. Eckel, MD, designated discussant for ARMMS-T2D at the session.
The results also showed notable rates of two adverse events associated with bariatric surgery: a 14% incidence of bone fractures, compared with a rate of 5% among controls, and a 12% incidence of anemia after surgery, compared with a rate of 3% among controls.
The control group also had a significantly higher 3% incidence of new need for hemodialysis, compared with no incident dialysis cases among the surgery patients.
“The fracture difference [after bariatric surgery] needs more careful follow-up,” commented Dr. Eckel, an endocrinologist and emeritus professor at the University of Colorado at Denver, Aurora.
ARMMS-T2D included data from 262 people with overweight or obesity and type 2 diabetes randomized in any of four U.S. studies that compared the outcomes of 166 patients who underwent bariatric surgery with 96 patients who served as controls and had lifestyle and medical interventions for weight loss and glycemic control. Seven-year follow-up included 82 (85%) of the initial 96 control patients and 136 (82%) of the initial 166 surgery patients. After 12 years, 31 of the controls (32%) and 83 surgery patients (50%) remained for the A1c analysis.
A quartet of studies joined together
The ARMMS-T2D prospective analysis resulted from an early partnership by the organizers of the four independent randomized studies that compared bariatric surgery with lifestyle and medical intervention in people with type 2 diabetes and overweight or obesity: STAMPEDE, which included 150 people at the Cleveland Clinic starting in 2007; SLIMM-T2D, which included 88 people at Brigham and Women’s Hospital and the Joslin Diabetes Center in Boston starting in 2010; TRIABETES, which included 69 people at the University of Pittsburgh starting in 2009; and CROSSROADS, which included 43 people at the University of Washington, Seattle, starting in 2011.
Further secondary findings from the ARMMS-T2D analyses showed that 38% of the surgery patients and 17% of controls had an A1c < 6.5% after 7 years.
At 7 years, type 2 diabetes remission, defined as those with an A1c < 6.5% who were not taking any antidiabetes medications, was reached in 18% of surgery patients and 6% of controls. At 12 years, 13% of the surgery patients and none of the controls met this metric, Dr. Courcoulas said.
The duration of diabetes a person had before undergoing bariatric surgery “may be an important factor” as to whether patients undergo remission, suggested Dr. Eckel. He noted that longer duration type 2 diabetes usually results in increased glucose intolerance and makes remission less likely
Roux-en-Y gastric bypass appeared to have the best rates of patients achieving both lower A1c levels and more weight loss, followed by sleeve gastrectomy and gastric banding, which had the worst performance. But Dr. Courcoulas cautioned that the study was underpowered to reliably compare individual surgical procedures.
In terms of those with an A1c < 7.0%, surgery patients maintained a steady prevalence rate of about 55% during the first 5 years of follow-up, roughly twice the rate of controls, at 28% during all years of follow-up starting at year 5.
About 37% of enrolled patients had a BMI < 35 kg/m2, and the A1c-lowering benefit and weight loss in this subgroup were consistent with the overall findings, which supports consideration of bariatric surgery for people with type 2 diabetes and a BMI < 35 kg/m2, Dr. Courcoulas said.
She also highlighted that bariatric surgery was linked with significant reductions in triglyceride levels and increased high-density lipoprotein cholesterol levels, compared with controls. However, 22% of surgery patients experienced abdominal pain, compared with 10% of controls, and 7% experienced dysphagia, compared with no cases among the controls.
ARMMS-T2D received no commercial funding. Dr. Courcoulas had no disclosures. Dr. Eckel has been a consultant to numerous companies but said he had no relevant disclosures.
A version of this article first appeared on Medscape.com.
SAN DIEGO – and a baseline body mass index (BMI) of at least 27 kg/m2, according to new study results.
The findings are from ARMMS-T2D, a prospective, controlled trial with the largest cohort and longest follow-up of bariatric surgery reported to date. The results reinforce the potential role of surgery “as an option to improve diabetes-related outcomes, including people with a BMI of less than 35 kg/m2,” said Anita P. Courcoulas, MD, at the recent annual scientific sessions of the American Diabetes Association.
People who underwent bariatric surgery (gastric band, sleeve gastrectomy, or Roux-en-Y gastric bypass) had an average 1.6–percentage point drop in hemoglobin A1c from baseline 7 years after surgery and an average 1.4–percentage point reduction from baseline after 12 years. Average decreases from baseline were 0.2 and 0.3 percentage points at these time points, respectively, among controls who underwent lifestyle and medical interventions only. Between-group differences were significant at both the 7-year (primary endpoint) and 12-year time points in the intention-to-treat analysis, reported Dr. Courcoulas, a professor of surgery at the University of Pittsburgh.
Average weight loss from baseline to 7 and 12 years was 19.9% and 19.3%, respectively, in the surgery group and 8.3% and 10.8%, respectively, among controls, which was significantly different between groups at both time points (a secondary endpoint).
Dr. Courcoulas highlighted that the 10.8% average weight loss after 12 years among controls included crossovers, with 25% of patients progressing from their initial intervention of lifestyle and medical management to undergoing bariatric surgery during follow-up. Among the controls who never underwent surgery (per-protocol analysis), the 12-year average weight loss from baseline was 7.3%.
High-dose incretin-hormone therapy missing
A major limitation of ARMMS-T2D (Alliance of Randomized Trials of Medicine vs. Metabolic Surgery in Type 2 Diabetes) is that it prospectively followed a combined cohort from four independently run controlled U.S. trials that all began more than a decade ago, before the contemporary era of medical weight loss management that’s been revolutionized by incretin-hormone receptor agonists such as semaglutide (Ozempic/Wegovy, Novo Nordisk) and tirzepatide (Mounjaro, Lilly).
New randomized, controlled trials “are needed” that compare metabolic bariatric surgery with medical and lifestyle management that includes “high-dose incretin-hormone therapy,” commented Robert H. Eckel, MD, designated discussant for ARMMS-T2D at the session.
The results also showed notable rates of two adverse events associated with bariatric surgery: a 14% incidence of bone fractures, compared with a rate of 5% among controls, and a 12% incidence of anemia after surgery, compared with a rate of 3% among controls.
The control group also had a significantly higher 3% incidence of new need for hemodialysis, compared with no incident dialysis cases among the surgery patients.
“The fracture difference [after bariatric surgery] needs more careful follow-up,” commented Dr. Eckel, an endocrinologist and emeritus professor at the University of Colorado at Denver, Aurora.
ARMMS-T2D included data from 262 people with overweight or obesity and type 2 diabetes randomized in any of four U.S. studies that compared the outcomes of 166 patients who underwent bariatric surgery with 96 patients who served as controls and had lifestyle and medical interventions for weight loss and glycemic control. Seven-year follow-up included 82 (85%) of the initial 96 control patients and 136 (82%) of the initial 166 surgery patients. After 12 years, 31 of the controls (32%) and 83 surgery patients (50%) remained for the A1c analysis.
A quartet of studies joined together
The ARMMS-T2D prospective analysis resulted from an early partnership by the organizers of the four independent randomized studies that compared bariatric surgery with lifestyle and medical intervention in people with type 2 diabetes and overweight or obesity: STAMPEDE, which included 150 people at the Cleveland Clinic starting in 2007; SLIMM-T2D, which included 88 people at Brigham and Women’s Hospital and the Joslin Diabetes Center in Boston starting in 2010; TRIABETES, which included 69 people at the University of Pittsburgh starting in 2009; and CROSSROADS, which included 43 people at the University of Washington, Seattle, starting in 2011.
Further secondary findings from the ARMMS-T2D analyses showed that 38% of the surgery patients and 17% of controls had an A1c < 6.5% after 7 years.
At 7 years, type 2 diabetes remission, defined as those with an A1c < 6.5% who were not taking any antidiabetes medications, was reached in 18% of surgery patients and 6% of controls. At 12 years, 13% of the surgery patients and none of the controls met this metric, Dr. Courcoulas said.
The duration of diabetes a person had before undergoing bariatric surgery “may be an important factor” as to whether patients undergo remission, suggested Dr. Eckel. He noted that longer duration type 2 diabetes usually results in increased glucose intolerance and makes remission less likely
Roux-en-Y gastric bypass appeared to have the best rates of patients achieving both lower A1c levels and more weight loss, followed by sleeve gastrectomy and gastric banding, which had the worst performance. But Dr. Courcoulas cautioned that the study was underpowered to reliably compare individual surgical procedures.
In terms of those with an A1c < 7.0%, surgery patients maintained a steady prevalence rate of about 55% during the first 5 years of follow-up, roughly twice the rate of controls, at 28% during all years of follow-up starting at year 5.
About 37% of enrolled patients had a BMI < 35 kg/m2, and the A1c-lowering benefit and weight loss in this subgroup were consistent with the overall findings, which supports consideration of bariatric surgery for people with type 2 diabetes and a BMI < 35 kg/m2, Dr. Courcoulas said.
She also highlighted that bariatric surgery was linked with significant reductions in triglyceride levels and increased high-density lipoprotein cholesterol levels, compared with controls. However, 22% of surgery patients experienced abdominal pain, compared with 10% of controls, and 7% experienced dysphagia, compared with no cases among the controls.
ARMMS-T2D received no commercial funding. Dr. Courcoulas had no disclosures. Dr. Eckel has been a consultant to numerous companies but said he had no relevant disclosures.
A version of this article first appeared on Medscape.com.
AT ADA 2023
Affording the cost of new obesity drugs? We can’t afford not to
SAN DIEGO – Although the glucagonlike peptide–1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, have been revolutionary advances for the treatment of obesity, the cost-effectiveness of these agents for treating both obesity and type 2 diabetes remains uncertain based on published analyses.
But potential future changes in the cost-effectiveness dynamics of GLP-1 agonists could tip the balance in their favor. These include
Costs to people with obesity that are generally not part of cost-effectiveness calculations include pain, disability, depression, and bias that affect employment, Carol H. Wysham, MD, said at the recent scientific sessions of the American Diabetes Association.
Other costs to society left out of conventional calculations are items such as the incremental cost for fuel to transport a heavier population and the carbon-footprint costs for the production and transportation of the excess food produced to feed an over-fed population, added Dr. Wysham, an endocrinologist with MultiCare and the Rockwood Clinic in Spokane, Wash.
Analyses should include ‘things we don’t often think about’
“The impact of living with obesity is much greater than what we traditionally calculate in health economics,” commented Naveed Sattar, PhD, speaking from the floor during the session.
“Patient happiness and self-esteem are hard to measure and capture as cost impacts. We need to also add carbon dioxide effects and transportation costs, and governments are starting to get wise to this. How to run proper health economics analyses is the key question; we need to do better than what we currently do,” said Dr. Sattar, a professor of metabolic medicine at the University of Glasgow.
Dr. Sattar is lead author of a recent analysis that highlights the overwhelming importance of improved weight management in adults as they age to reduce their risk of developing a broad range of chronic disorders.
“Most chronic conditions are, to differing extents, caused or exacerbated by excess adiposity,” was a conclusion of his report.
“It’s important to include the costs to society, including things we don’t often think about. No one has ever done a cost analysis that includes all the factors” cited by Dr. Wysham, said Irl B. Hirsch, MD, another speaker at the session. “No one includes obstructive sleep apnea, degenerative arthritis, and the downstream effects of a high body mass index.”
The GLP-1 agonists “are great” for both weight loss and glycemic control, said Dr. Hirsch, an endocrinologist and professor at the University of Washington, Seattle. “We can’t afford not to use them. These agents have been transformational.”
U.S. has the highest drug costs
Another key factor driving cost-effectiveness is, of course, the relatively high cost of the agents in the class, especially in the United States. Dr. Hirsch cited a recently published report in Obesity that quoted monthly U.S. costs of $804 for weekly 2.4-mg injections of semaglutide (Wegovy) and $1418 for daily 3.0-mg injections of liraglutide (Saxenda). Highlighting the relatively high cost of medications in the United States, the report cited a monthly price tag of $95 for the same semaglutide regimen in Turkey and a monthly cost of $252 for the same liraglutide regimen in Norway.
U.S. prices for agents in this class may start to deflate as soon as 2024, when one or more generic versions of liraglutide are expected, following expiration of the U.S. patent later in 2023, Dr. Wysham said.
Another pending trigger for lower costs may be the possible decision by the World Health Organization to designate liraglutide an “essential medicine” later in 2023, she noted. The WHO received an application for this designation from four U.S. clinicians and is considering it as part of its planned 2023 update to the WHO’s Essential Medicines List. Dr. Wysham predicted this designation would “press international pharmaceutical companies to produce [liraglutide] at a much lower cost.”
“I’m not saying that drug companies should not profit, but they should not do it on the backs of patients,” Dr. Wysham declared. “What do we measure by ‘cost-effectiveness?’ There are so many complications of obesity. For patients with diabetes and obesity we need to look for a little different economic policy.”
Dr. Wysham has reported being an adviser to Abbott and CeQur and receiving research funding from Eli Lilly and Novo Nordisk. Dr. Hirsch has reported being a consultant for Abbott, Embecta, and Hagar, and receiving research funding from Dexcom and Insulet. Dr. Sattar has reported receiving consulting fees or speaker honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.
A version of this article appeared on Medscape.com.
SAN DIEGO – Although the glucagonlike peptide–1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, have been revolutionary advances for the treatment of obesity, the cost-effectiveness of these agents for treating both obesity and type 2 diabetes remains uncertain based on published analyses.
But potential future changes in the cost-effectiveness dynamics of GLP-1 agonists could tip the balance in their favor. These include
Costs to people with obesity that are generally not part of cost-effectiveness calculations include pain, disability, depression, and bias that affect employment, Carol H. Wysham, MD, said at the recent scientific sessions of the American Diabetes Association.
Other costs to society left out of conventional calculations are items such as the incremental cost for fuel to transport a heavier population and the carbon-footprint costs for the production and transportation of the excess food produced to feed an over-fed population, added Dr. Wysham, an endocrinologist with MultiCare and the Rockwood Clinic in Spokane, Wash.
Analyses should include ‘things we don’t often think about’
“The impact of living with obesity is much greater than what we traditionally calculate in health economics,” commented Naveed Sattar, PhD, speaking from the floor during the session.
“Patient happiness and self-esteem are hard to measure and capture as cost impacts. We need to also add carbon dioxide effects and transportation costs, and governments are starting to get wise to this. How to run proper health economics analyses is the key question; we need to do better than what we currently do,” said Dr. Sattar, a professor of metabolic medicine at the University of Glasgow.
Dr. Sattar is lead author of a recent analysis that highlights the overwhelming importance of improved weight management in adults as they age to reduce their risk of developing a broad range of chronic disorders.
“Most chronic conditions are, to differing extents, caused or exacerbated by excess adiposity,” was a conclusion of his report.
“It’s important to include the costs to society, including things we don’t often think about. No one has ever done a cost analysis that includes all the factors” cited by Dr. Wysham, said Irl B. Hirsch, MD, another speaker at the session. “No one includes obstructive sleep apnea, degenerative arthritis, and the downstream effects of a high body mass index.”
The GLP-1 agonists “are great” for both weight loss and glycemic control, said Dr. Hirsch, an endocrinologist and professor at the University of Washington, Seattle. “We can’t afford not to use them. These agents have been transformational.”
U.S. has the highest drug costs
Another key factor driving cost-effectiveness is, of course, the relatively high cost of the agents in the class, especially in the United States. Dr. Hirsch cited a recently published report in Obesity that quoted monthly U.S. costs of $804 for weekly 2.4-mg injections of semaglutide (Wegovy) and $1418 for daily 3.0-mg injections of liraglutide (Saxenda). Highlighting the relatively high cost of medications in the United States, the report cited a monthly price tag of $95 for the same semaglutide regimen in Turkey and a monthly cost of $252 for the same liraglutide regimen in Norway.
U.S. prices for agents in this class may start to deflate as soon as 2024, when one or more generic versions of liraglutide are expected, following expiration of the U.S. patent later in 2023, Dr. Wysham said.
Another pending trigger for lower costs may be the possible decision by the World Health Organization to designate liraglutide an “essential medicine” later in 2023, she noted. The WHO received an application for this designation from four U.S. clinicians and is considering it as part of its planned 2023 update to the WHO’s Essential Medicines List. Dr. Wysham predicted this designation would “press international pharmaceutical companies to produce [liraglutide] at a much lower cost.”
“I’m not saying that drug companies should not profit, but they should not do it on the backs of patients,” Dr. Wysham declared. “What do we measure by ‘cost-effectiveness?’ There are so many complications of obesity. For patients with diabetes and obesity we need to look for a little different economic policy.”
Dr. Wysham has reported being an adviser to Abbott and CeQur and receiving research funding from Eli Lilly and Novo Nordisk. Dr. Hirsch has reported being a consultant for Abbott, Embecta, and Hagar, and receiving research funding from Dexcom and Insulet. Dr. Sattar has reported receiving consulting fees or speaker honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.
A version of this article appeared on Medscape.com.
SAN DIEGO – Although the glucagonlike peptide–1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, have been revolutionary advances for the treatment of obesity, the cost-effectiveness of these agents for treating both obesity and type 2 diabetes remains uncertain based on published analyses.
But potential future changes in the cost-effectiveness dynamics of GLP-1 agonists could tip the balance in their favor. These include
Costs to people with obesity that are generally not part of cost-effectiveness calculations include pain, disability, depression, and bias that affect employment, Carol H. Wysham, MD, said at the recent scientific sessions of the American Diabetes Association.
Other costs to society left out of conventional calculations are items such as the incremental cost for fuel to transport a heavier population and the carbon-footprint costs for the production and transportation of the excess food produced to feed an over-fed population, added Dr. Wysham, an endocrinologist with MultiCare and the Rockwood Clinic in Spokane, Wash.
Analyses should include ‘things we don’t often think about’
“The impact of living with obesity is much greater than what we traditionally calculate in health economics,” commented Naveed Sattar, PhD, speaking from the floor during the session.
“Patient happiness and self-esteem are hard to measure and capture as cost impacts. We need to also add carbon dioxide effects and transportation costs, and governments are starting to get wise to this. How to run proper health economics analyses is the key question; we need to do better than what we currently do,” said Dr. Sattar, a professor of metabolic medicine at the University of Glasgow.
Dr. Sattar is lead author of a recent analysis that highlights the overwhelming importance of improved weight management in adults as they age to reduce their risk of developing a broad range of chronic disorders.
“Most chronic conditions are, to differing extents, caused or exacerbated by excess adiposity,” was a conclusion of his report.
“It’s important to include the costs to society, including things we don’t often think about. No one has ever done a cost analysis that includes all the factors” cited by Dr. Wysham, said Irl B. Hirsch, MD, another speaker at the session. “No one includes obstructive sleep apnea, degenerative arthritis, and the downstream effects of a high body mass index.”
The GLP-1 agonists “are great” for both weight loss and glycemic control, said Dr. Hirsch, an endocrinologist and professor at the University of Washington, Seattle. “We can’t afford not to use them. These agents have been transformational.”
U.S. has the highest drug costs
Another key factor driving cost-effectiveness is, of course, the relatively high cost of the agents in the class, especially in the United States. Dr. Hirsch cited a recently published report in Obesity that quoted monthly U.S. costs of $804 for weekly 2.4-mg injections of semaglutide (Wegovy) and $1418 for daily 3.0-mg injections of liraglutide (Saxenda). Highlighting the relatively high cost of medications in the United States, the report cited a monthly price tag of $95 for the same semaglutide regimen in Turkey and a monthly cost of $252 for the same liraglutide regimen in Norway.
U.S. prices for agents in this class may start to deflate as soon as 2024, when one or more generic versions of liraglutide are expected, following expiration of the U.S. patent later in 2023, Dr. Wysham said.
Another pending trigger for lower costs may be the possible decision by the World Health Organization to designate liraglutide an “essential medicine” later in 2023, she noted. The WHO received an application for this designation from four U.S. clinicians and is considering it as part of its planned 2023 update to the WHO’s Essential Medicines List. Dr. Wysham predicted this designation would “press international pharmaceutical companies to produce [liraglutide] at a much lower cost.”
“I’m not saying that drug companies should not profit, but they should not do it on the backs of patients,” Dr. Wysham declared. “What do we measure by ‘cost-effectiveness?’ There are so many complications of obesity. For patients with diabetes and obesity we need to look for a little different economic policy.”
Dr. Wysham has reported being an adviser to Abbott and CeQur and receiving research funding from Eli Lilly and Novo Nordisk. Dr. Hirsch has reported being a consultant for Abbott, Embecta, and Hagar, and receiving research funding from Dexcom and Insulet. Dr. Sattar has reported receiving consulting fees or speaker honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.
A version of this article appeared on Medscape.com.
AT ADA 2023
Debate: Initial combination therapy for type 2 diabetes?
SAN DIEGO –
This question was debated by two well-known clinician-researchers in the diabetes world at the recent annual scientific sessions of the American Diabetes Association.
Ralph A. DeFronzo, MD, argued for combination therapy at the time of diagnosis, and David M. Nathan, MD, countered that sequential therapy is a better way to go.
‘The ominous octet’: Addressing multiple underlying defects
Of course, Dr. DeFronzo said, the right agents must be selected. “The drugs we’re going to use as combination at a minimum have to correct the underlying insulin resistance and beta-cell failure, or we are not going to be successful.”
In addition, he said, these drugs should also provide protection against cardiovascular, kidney, and fatty liver disease, because “[managing] diabetes is more than just controlling the glucose.”
Recent U.S. data suggest that half of people with diabetes have a hemoglobin A1c above 7%, and a quarter remain above 8%. “We’re not really doing a very good job in terms of glycemic control,” said Dr. DeFronzo, chief of the diabetes division at University of Texas, San Antonio.
One reason for this failure, he said, is the complex pathophysiology of type 2 diabetes represented by eight major defects, what he called the “ominous octet”: decreased pancreatic insulin secretion, gut incretin effects, glucose uptake in the muscle, increased lipolysis, glucose reabsorption in the kidney, hepatic glucose production, increased glucagon secretion, and neurotransmitter dysfunction.
“There are eight problems, so you’re going to need multiple drugs in combination ... not ones that just lower the A1c.”
And, Dr. DeFronzo said, these drugs “must be started early in the natural history of type 2 diabetes if progressive beta-cell failure is to be prevented.”
He pointed to the United Kingdom Prospective Diabetes Study (UKPDS), in which the sulfonylurea glyburide was used first, followed by metformin. With each drug, the A1c decreased initially but then rose within 3 years. By 15 years, 65% of participants were taking insulin.
More recently, the GRADE study examined the effects of adding four different glucose-lowering agents (glimepiride, sitagliptin, liraglutide, or insulin glargine) in people who hadn’t achieved target A1c with metformin.
“So, by definition, drug number one failed,” he observed.
During the study, all participants showed an initial A1c drop, followed by progressive failure, “again ... showing that stepwise therapy doesn’t work.”
All patients with type 2 diabetes at his center are treated using the “DeFronzo algorithm” consisting of three drug classes: a glucagon-like peptide-1 (GLP-1) agonist, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, and pioglitazone, as each of them targets more than one of the “ominous octet” defects.
“The drugs that clearly do not work on a long-term basis are metformin and sulfonylureas,” he emphasized.
Several studies demonstrate the efficacy of combination therapy, he said. In one, DURATION 8, the combination of exenatide and dapagliflozin was superior to either agent individually in lowering A1c, cardiovascular events, and all-cause mortality over 2 years.
And in the 5-year VERIFY study, early combination therapy with vildagliptin plus metformin proved superior in A1c-lowering to starting patients on metformin and adding vildagliptin later.
Dr. DeFronzo’s own “knock-out punch” study, EDICT, in people with new-onset type 2 diabetes, compared the initial combination of metformin, pioglitazone, and exenatide with conventional sequential add-on therapy with metformin, glipizide, and insulin glargine.
The primary endpoint – the difference in the proportion of patients with A1c less than 6.5% – was 70% versus 29% with combination compared with sequential therapy, a difference “as robust as you can be going against the stepwise approach” at P < .00001, he said.
The combination therapy virtually normalized both insulin sensitivity and beta-cell function, whereas the conventional therapy did neither.
Also from Dr. DeFronzo’s group, in the Qatar study, which compared exenatide plus pioglitazone with basal-bolus insulin in people with about 10 years’ duration of type 2 diabetes and A1c above 7.5% taking sulfonylurea plus metformin, the combination therapy produced an A1c of 6.2% versus 7.1% with insulin.
Dr. DeFronzo pointed to new language added to the ADA Standards of Medical Care in Diabetes in 2022.
While still endorsing stepwise therapy, the document also says that “there are data to support initial combination therapy for more rapid attainment of glycemic targets and longer durability of glycemic effect.” The two references cited are EDICT and VERIFY.
“Finally, the American Diabetes Association has gotten the message,” he concluded.
Sequential therapy: Far more data, lower cost
Dr. Nathan began by pointing out that the ADA Standards of Care continue to advise use of metformin as first-line therapy for type 2 diabetes “because of its high efficacy in lowering A1c, minimal hypoglycemia risk when used as monotherapy, weight neutrality with the potential for modest weight loss, good safety profile, and low cost.”
He emphasized that he was not arguing “against the use of early or even initial combination therapy when there are co-existent morbidities [such as cardiovascular or chronic kidney disease] that merit use of demonstrably effective medications.” But Dr. Nathan pointed out, those patients are not the majority with type 2 diabetes.
He laid out four main arguments for choosing traditional sequential therapy over initial combination therapy. For one, it “enables determination of efficacy of adding individual medications, while initial combination precludes determining benefits of individual drugs.”
Second, traditional sequential therapy allows for assessment of side effects from individual drugs.
“With Dr. DeFronzo’s algorithm you throw everything at them, and if they get nausea, vomiting, or diarrhea, you won’t know which drug it is ... If they get an allergic reaction, you won’t know which medication it is,” observed Dr. Nathan, who is director of the clinical research center and the diabetes center at Massachusetts General Hospital, Boston.
Moreover, he said, traditional sequential therapy “promotes individualization, with selection of drugs, which is something we’re laboring to achieve. Initial combination obviously limits that.”
Further, sequential therapy is “parsimonious and cost-effective, whereas initial combination therapy is expensive, with modest advantages at most.”
And, there are “lots of data” supporting traditional sequential therapy and relatively little for initial combination therapy.
Dr. Nathan added that when he searched the literature for relevant randomized clinical trials, he found 16 investigating initial combination therapy versus monotherapy, but only three that examined combination versus sequential therapy.
“Very few of them, except for EDICT and VERIFY, actually include the sequential therapy that we would use in practice,” he said.
Moreover, he observed, except for the VERIFY study, most are less than half a year in duration. And in VERIFY, there was an initial 20% difference in the proportions of patients with A1c below 7.0%, but by 12 months, that difference had shrunk to just 5%-6%.
“So, looking over time is very important,” Dr. Nathan cautioned. “We really have to be careful ... Six months is barely enough time to see A1c equilibrate ... You really need to study a long-term, chronic, progressive disease like type 2 diabetes over a long enough period of time to be clinically meaningful.”
Dr. Nathan acknowledged to Dr. DeFronzo that the latter’s EDICT study was “well conducted” and “long enough,” and that the researchers did examine monotherapy versus sequential therapy. However, he pointed out that it was a small study with 249 patients and the dropout rate was high, with 58% of patients remaining in the study with triple therapy versus 68% for conventional treatment. “That’s a bit problematic,” Dr. Nathan noted.
At 2 years, the “trivial” difference in A1c was 6.5% with conventional therapy versus 6.0% with triple therapy. “This is all on the very flat complications curve with regard to A1c,” he observed.
Patients treated with sequential therapy with sulfonylurea and insulin had higher rates of hypoglycemia and weight gain, whereas the combination triple therapy group had more gastrointestinal side effects and edema.
However, the most dramatic difference was cost: the average wholesale price for sequential therapy totaled about $85 per month, compared with $1,310 for initial combination therapy. For the approximately 1.5 million patients with new-onset type 2 diabetes in the United States, that difference comes to an additional cost per year of about $22 billion, Dr. Nathan calculated.
“Although current sequential therapy leaves much to be desired ... initial combination therapy has generally only been tested for brief, clinically insufficient periods.
“And therefore, I think sequential therapy is still what is called for,” he concluded. “Well-powered, acceptable-duration studies need to be performed before we can adopt initial/early combination therapy as the standard of care.”
Dr. DeFronzo has reported receiving research support from Boehringer Ingelheim, AstraZeneca, and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca; and participation on a data safety monitoring board or advisory board for AstraZeneca, Intarcia, Novo Nordisk, and Boehringer Ingelheim. Dr. Nathan has reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
SAN DIEGO –
This question was debated by two well-known clinician-researchers in the diabetes world at the recent annual scientific sessions of the American Diabetes Association.
Ralph A. DeFronzo, MD, argued for combination therapy at the time of diagnosis, and David M. Nathan, MD, countered that sequential therapy is a better way to go.
‘The ominous octet’: Addressing multiple underlying defects
Of course, Dr. DeFronzo said, the right agents must be selected. “The drugs we’re going to use as combination at a minimum have to correct the underlying insulin resistance and beta-cell failure, or we are not going to be successful.”
In addition, he said, these drugs should also provide protection against cardiovascular, kidney, and fatty liver disease, because “[managing] diabetes is more than just controlling the glucose.”
Recent U.S. data suggest that half of people with diabetes have a hemoglobin A1c above 7%, and a quarter remain above 8%. “We’re not really doing a very good job in terms of glycemic control,” said Dr. DeFronzo, chief of the diabetes division at University of Texas, San Antonio.
One reason for this failure, he said, is the complex pathophysiology of type 2 diabetes represented by eight major defects, what he called the “ominous octet”: decreased pancreatic insulin secretion, gut incretin effects, glucose uptake in the muscle, increased lipolysis, glucose reabsorption in the kidney, hepatic glucose production, increased glucagon secretion, and neurotransmitter dysfunction.
“There are eight problems, so you’re going to need multiple drugs in combination ... not ones that just lower the A1c.”
And, Dr. DeFronzo said, these drugs “must be started early in the natural history of type 2 diabetes if progressive beta-cell failure is to be prevented.”
He pointed to the United Kingdom Prospective Diabetes Study (UKPDS), in which the sulfonylurea glyburide was used first, followed by metformin. With each drug, the A1c decreased initially but then rose within 3 years. By 15 years, 65% of participants were taking insulin.
More recently, the GRADE study examined the effects of adding four different glucose-lowering agents (glimepiride, sitagliptin, liraglutide, or insulin glargine) in people who hadn’t achieved target A1c with metformin.
“So, by definition, drug number one failed,” he observed.
During the study, all participants showed an initial A1c drop, followed by progressive failure, “again ... showing that stepwise therapy doesn’t work.”
All patients with type 2 diabetes at his center are treated using the “DeFronzo algorithm” consisting of three drug classes: a glucagon-like peptide-1 (GLP-1) agonist, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, and pioglitazone, as each of them targets more than one of the “ominous octet” defects.
“The drugs that clearly do not work on a long-term basis are metformin and sulfonylureas,” he emphasized.
Several studies demonstrate the efficacy of combination therapy, he said. In one, DURATION 8, the combination of exenatide and dapagliflozin was superior to either agent individually in lowering A1c, cardiovascular events, and all-cause mortality over 2 years.
And in the 5-year VERIFY study, early combination therapy with vildagliptin plus metformin proved superior in A1c-lowering to starting patients on metformin and adding vildagliptin later.
Dr. DeFronzo’s own “knock-out punch” study, EDICT, in people with new-onset type 2 diabetes, compared the initial combination of metformin, pioglitazone, and exenatide with conventional sequential add-on therapy with metformin, glipizide, and insulin glargine.
The primary endpoint – the difference in the proportion of patients with A1c less than 6.5% – was 70% versus 29% with combination compared with sequential therapy, a difference “as robust as you can be going against the stepwise approach” at P < .00001, he said.
The combination therapy virtually normalized both insulin sensitivity and beta-cell function, whereas the conventional therapy did neither.
Also from Dr. DeFronzo’s group, in the Qatar study, which compared exenatide plus pioglitazone with basal-bolus insulin in people with about 10 years’ duration of type 2 diabetes and A1c above 7.5% taking sulfonylurea plus metformin, the combination therapy produced an A1c of 6.2% versus 7.1% with insulin.
Dr. DeFronzo pointed to new language added to the ADA Standards of Medical Care in Diabetes in 2022.
While still endorsing stepwise therapy, the document also says that “there are data to support initial combination therapy for more rapid attainment of glycemic targets and longer durability of glycemic effect.” The two references cited are EDICT and VERIFY.
“Finally, the American Diabetes Association has gotten the message,” he concluded.
Sequential therapy: Far more data, lower cost
Dr. Nathan began by pointing out that the ADA Standards of Care continue to advise use of metformin as first-line therapy for type 2 diabetes “because of its high efficacy in lowering A1c, minimal hypoglycemia risk when used as monotherapy, weight neutrality with the potential for modest weight loss, good safety profile, and low cost.”
He emphasized that he was not arguing “against the use of early or even initial combination therapy when there are co-existent morbidities [such as cardiovascular or chronic kidney disease] that merit use of demonstrably effective medications.” But Dr. Nathan pointed out, those patients are not the majority with type 2 diabetes.
He laid out four main arguments for choosing traditional sequential therapy over initial combination therapy. For one, it “enables determination of efficacy of adding individual medications, while initial combination precludes determining benefits of individual drugs.”
Second, traditional sequential therapy allows for assessment of side effects from individual drugs.
“With Dr. DeFronzo’s algorithm you throw everything at them, and if they get nausea, vomiting, or diarrhea, you won’t know which drug it is ... If they get an allergic reaction, you won’t know which medication it is,” observed Dr. Nathan, who is director of the clinical research center and the diabetes center at Massachusetts General Hospital, Boston.
Moreover, he said, traditional sequential therapy “promotes individualization, with selection of drugs, which is something we’re laboring to achieve. Initial combination obviously limits that.”
Further, sequential therapy is “parsimonious and cost-effective, whereas initial combination therapy is expensive, with modest advantages at most.”
And, there are “lots of data” supporting traditional sequential therapy and relatively little for initial combination therapy.
Dr. Nathan added that when he searched the literature for relevant randomized clinical trials, he found 16 investigating initial combination therapy versus monotherapy, but only three that examined combination versus sequential therapy.
“Very few of them, except for EDICT and VERIFY, actually include the sequential therapy that we would use in practice,” he said.
Moreover, he observed, except for the VERIFY study, most are less than half a year in duration. And in VERIFY, there was an initial 20% difference in the proportions of patients with A1c below 7.0%, but by 12 months, that difference had shrunk to just 5%-6%.
“So, looking over time is very important,” Dr. Nathan cautioned. “We really have to be careful ... Six months is barely enough time to see A1c equilibrate ... You really need to study a long-term, chronic, progressive disease like type 2 diabetes over a long enough period of time to be clinically meaningful.”
Dr. Nathan acknowledged to Dr. DeFronzo that the latter’s EDICT study was “well conducted” and “long enough,” and that the researchers did examine monotherapy versus sequential therapy. However, he pointed out that it was a small study with 249 patients and the dropout rate was high, with 58% of patients remaining in the study with triple therapy versus 68% for conventional treatment. “That’s a bit problematic,” Dr. Nathan noted.
At 2 years, the “trivial” difference in A1c was 6.5% with conventional therapy versus 6.0% with triple therapy. “This is all on the very flat complications curve with regard to A1c,” he observed.
Patients treated with sequential therapy with sulfonylurea and insulin had higher rates of hypoglycemia and weight gain, whereas the combination triple therapy group had more gastrointestinal side effects and edema.
However, the most dramatic difference was cost: the average wholesale price for sequential therapy totaled about $85 per month, compared with $1,310 for initial combination therapy. For the approximately 1.5 million patients with new-onset type 2 diabetes in the United States, that difference comes to an additional cost per year of about $22 billion, Dr. Nathan calculated.
“Although current sequential therapy leaves much to be desired ... initial combination therapy has generally only been tested for brief, clinically insufficient periods.
“And therefore, I think sequential therapy is still what is called for,” he concluded. “Well-powered, acceptable-duration studies need to be performed before we can adopt initial/early combination therapy as the standard of care.”
Dr. DeFronzo has reported receiving research support from Boehringer Ingelheim, AstraZeneca, and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca; and participation on a data safety monitoring board or advisory board for AstraZeneca, Intarcia, Novo Nordisk, and Boehringer Ingelheim. Dr. Nathan has reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
SAN DIEGO –
This question was debated by two well-known clinician-researchers in the diabetes world at the recent annual scientific sessions of the American Diabetes Association.
Ralph A. DeFronzo, MD, argued for combination therapy at the time of diagnosis, and David M. Nathan, MD, countered that sequential therapy is a better way to go.
‘The ominous octet’: Addressing multiple underlying defects
Of course, Dr. DeFronzo said, the right agents must be selected. “The drugs we’re going to use as combination at a minimum have to correct the underlying insulin resistance and beta-cell failure, or we are not going to be successful.”
In addition, he said, these drugs should also provide protection against cardiovascular, kidney, and fatty liver disease, because “[managing] diabetes is more than just controlling the glucose.”
Recent U.S. data suggest that half of people with diabetes have a hemoglobin A1c above 7%, and a quarter remain above 8%. “We’re not really doing a very good job in terms of glycemic control,” said Dr. DeFronzo, chief of the diabetes division at University of Texas, San Antonio.
One reason for this failure, he said, is the complex pathophysiology of type 2 diabetes represented by eight major defects, what he called the “ominous octet”: decreased pancreatic insulin secretion, gut incretin effects, glucose uptake in the muscle, increased lipolysis, glucose reabsorption in the kidney, hepatic glucose production, increased glucagon secretion, and neurotransmitter dysfunction.
“There are eight problems, so you’re going to need multiple drugs in combination ... not ones that just lower the A1c.”
And, Dr. DeFronzo said, these drugs “must be started early in the natural history of type 2 diabetes if progressive beta-cell failure is to be prevented.”
He pointed to the United Kingdom Prospective Diabetes Study (UKPDS), in which the sulfonylurea glyburide was used first, followed by metformin. With each drug, the A1c decreased initially but then rose within 3 years. By 15 years, 65% of participants were taking insulin.
More recently, the GRADE study examined the effects of adding four different glucose-lowering agents (glimepiride, sitagliptin, liraglutide, or insulin glargine) in people who hadn’t achieved target A1c with metformin.
“So, by definition, drug number one failed,” he observed.
During the study, all participants showed an initial A1c drop, followed by progressive failure, “again ... showing that stepwise therapy doesn’t work.”
All patients with type 2 diabetes at his center are treated using the “DeFronzo algorithm” consisting of three drug classes: a glucagon-like peptide-1 (GLP-1) agonist, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, and pioglitazone, as each of them targets more than one of the “ominous octet” defects.
“The drugs that clearly do not work on a long-term basis are metformin and sulfonylureas,” he emphasized.
Several studies demonstrate the efficacy of combination therapy, he said. In one, DURATION 8, the combination of exenatide and dapagliflozin was superior to either agent individually in lowering A1c, cardiovascular events, and all-cause mortality over 2 years.
And in the 5-year VERIFY study, early combination therapy with vildagliptin plus metformin proved superior in A1c-lowering to starting patients on metformin and adding vildagliptin later.
Dr. DeFronzo’s own “knock-out punch” study, EDICT, in people with new-onset type 2 diabetes, compared the initial combination of metformin, pioglitazone, and exenatide with conventional sequential add-on therapy with metformin, glipizide, and insulin glargine.
The primary endpoint – the difference in the proportion of patients with A1c less than 6.5% – was 70% versus 29% with combination compared with sequential therapy, a difference “as robust as you can be going against the stepwise approach” at P < .00001, he said.
The combination therapy virtually normalized both insulin sensitivity and beta-cell function, whereas the conventional therapy did neither.
Also from Dr. DeFronzo’s group, in the Qatar study, which compared exenatide plus pioglitazone with basal-bolus insulin in people with about 10 years’ duration of type 2 diabetes and A1c above 7.5% taking sulfonylurea plus metformin, the combination therapy produced an A1c of 6.2% versus 7.1% with insulin.
Dr. DeFronzo pointed to new language added to the ADA Standards of Medical Care in Diabetes in 2022.
While still endorsing stepwise therapy, the document also says that “there are data to support initial combination therapy for more rapid attainment of glycemic targets and longer durability of glycemic effect.” The two references cited are EDICT and VERIFY.
“Finally, the American Diabetes Association has gotten the message,” he concluded.
Sequential therapy: Far more data, lower cost
Dr. Nathan began by pointing out that the ADA Standards of Care continue to advise use of metformin as first-line therapy for type 2 diabetes “because of its high efficacy in lowering A1c, minimal hypoglycemia risk when used as monotherapy, weight neutrality with the potential for modest weight loss, good safety profile, and low cost.”
He emphasized that he was not arguing “against the use of early or even initial combination therapy when there are co-existent morbidities [such as cardiovascular or chronic kidney disease] that merit use of demonstrably effective medications.” But Dr. Nathan pointed out, those patients are not the majority with type 2 diabetes.
He laid out four main arguments for choosing traditional sequential therapy over initial combination therapy. For one, it “enables determination of efficacy of adding individual medications, while initial combination precludes determining benefits of individual drugs.”
Second, traditional sequential therapy allows for assessment of side effects from individual drugs.
“With Dr. DeFronzo’s algorithm you throw everything at them, and if they get nausea, vomiting, or diarrhea, you won’t know which drug it is ... If they get an allergic reaction, you won’t know which medication it is,” observed Dr. Nathan, who is director of the clinical research center and the diabetes center at Massachusetts General Hospital, Boston.
Moreover, he said, traditional sequential therapy “promotes individualization, with selection of drugs, which is something we’re laboring to achieve. Initial combination obviously limits that.”
Further, sequential therapy is “parsimonious and cost-effective, whereas initial combination therapy is expensive, with modest advantages at most.”
And, there are “lots of data” supporting traditional sequential therapy and relatively little for initial combination therapy.
Dr. Nathan added that when he searched the literature for relevant randomized clinical trials, he found 16 investigating initial combination therapy versus monotherapy, but only three that examined combination versus sequential therapy.
“Very few of them, except for EDICT and VERIFY, actually include the sequential therapy that we would use in practice,” he said.
Moreover, he observed, except for the VERIFY study, most are less than half a year in duration. And in VERIFY, there was an initial 20% difference in the proportions of patients with A1c below 7.0%, but by 12 months, that difference had shrunk to just 5%-6%.
“So, looking over time is very important,” Dr. Nathan cautioned. “We really have to be careful ... Six months is barely enough time to see A1c equilibrate ... You really need to study a long-term, chronic, progressive disease like type 2 diabetes over a long enough period of time to be clinically meaningful.”
Dr. Nathan acknowledged to Dr. DeFronzo that the latter’s EDICT study was “well conducted” and “long enough,” and that the researchers did examine monotherapy versus sequential therapy. However, he pointed out that it was a small study with 249 patients and the dropout rate was high, with 58% of patients remaining in the study with triple therapy versus 68% for conventional treatment. “That’s a bit problematic,” Dr. Nathan noted.
At 2 years, the “trivial” difference in A1c was 6.5% with conventional therapy versus 6.0% with triple therapy. “This is all on the very flat complications curve with regard to A1c,” he observed.
Patients treated with sequential therapy with sulfonylurea and insulin had higher rates of hypoglycemia and weight gain, whereas the combination triple therapy group had more gastrointestinal side effects and edema.
However, the most dramatic difference was cost: the average wholesale price for sequential therapy totaled about $85 per month, compared with $1,310 for initial combination therapy. For the approximately 1.5 million patients with new-onset type 2 diabetes in the United States, that difference comes to an additional cost per year of about $22 billion, Dr. Nathan calculated.
“Although current sequential therapy leaves much to be desired ... initial combination therapy has generally only been tested for brief, clinically insufficient periods.
“And therefore, I think sequential therapy is still what is called for,” he concluded. “Well-powered, acceptable-duration studies need to be performed before we can adopt initial/early combination therapy as the standard of care.”
Dr. DeFronzo has reported receiving research support from Boehringer Ingelheim, AstraZeneca, and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca; and participation on a data safety monitoring board or advisory board for AstraZeneca, Intarcia, Novo Nordisk, and Boehringer Ingelheim. Dr. Nathan has reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Aging and type 1 diabetes: ‘Complete picture’ 40 years on
SAN DIEGO –
New funding for 2022-2027 for the DCCT long-term observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) will go toward investigating aspects of type 1 diabetes that are associated with aging and are also common in type 2 diabetes, including cardiovascular disease, fatty liver disease, and sleep apnea.
The original randomized DCCT clinical trial results, published in 1993 in the New England Journal of Medicine, proved that early intensive glycemic control was the key to preventing or slowing the progression of long-term eye, kidney, and nerve complications of type 1 diabetes. Subsequently, EDIC has yielded many more major findings including that early tight glycemic control also reduces cardiovascular risk and prolongs survival in type 1 diabetes.
And although the phenomenon of metabolic memory initially seen in EDIC means that early glycemic control is important, subsequent EDIC data also have suggested that it is never too late to initiate intensive glycemic control, speakers emphasized during a special symposium commemorating 40 years since the start of DCCT, held during the annual scientific sessions of the American Diabetes Association. As with the 30-year DCCT/EDIC commemorative symposium held in 2013, local study participants were in the audience and were acknowledged with long applause.
Together, DCCT and EDIC – both funded by the National Institutes of Health at 27 sites in the United States and Canada – have changed the standard of care for people with type 1 diabetes and continue to inform clinical practice. Prior to the DCCT, between 1930 and 1970, about a third of people with type 1 diabetes developed vision loss and one in five experienced kidney failure and/or myocardial infarction. Stroke and amputation were also common, DCCT/EDIC chair David M. Nathan, MD, said while introducing the symposium.
“All of the advances in care of type 1 diabetes have developed because this study demonstrated that it was important – continuous glucose monitoring (CGM), new insulins, better [insulin] pumps. ... I think the most profound finding is that mortality in our intensively treated cohort is the same as in the general population. That says it all,” Dr. Nathan said in an interview.
And now, “what we still have yet to contribute is what happens to type 1 diabetes as people get older,” added Dr. Nathan, a professor of medicine at Harvard Medical School and director of the Diabetes Center at Massachusetts General Hospital, both in Boston.
‘Something that heretofore none of us could have imagined’
The 1,441 DCCT participants had a mean age of 27 years at baseline in 1983, when they were randomized to intensive insulin therapy or usual care. The 1,375 participants (96%) who continued into EDIC in 1994 were an average of 35 years old at that point, when the usual care group was taught intensive glycemic management and all participants returned to their personal health care teams. The 1,075 participants in EDIC today are an average age of 63 years.
Only 11 participants had died at the start of EDIC, and just 250 (17%) have died as of 2023, said study coordinator cochair Gayle Lorenzi, RN, who is a certified diabetes care and education specialist at the University of California, San Diego.
“DCCT/EDIC because of its longevity represents a unique opportunity to explore aging in long duration of type 1 diabetes, something that heretofore none of us could have imagined, especially for those of you in the audience who started your careers in the 70s and 80s,” Ms. Lorenzi commented.
About 36% of the cohort now has overweight and 40% have obesity, mirroring the general population. And they now have a mean hemoglobin A1c of 7.3%.
According to Barbara H. Braffett, PhD, co–principal investigator at the DCCT/EDIC data coordinating center: “The EDIC study is now shifting its focus during the next 5 years to understand the clinical course of type 1 diabetes in the setting of advancing duration and age, as well as increasing adiposity, which has progressively affected individuals with type 1 diabetes and has potential long-term adverse consequences.”
Dr. Braffett outlined the new study approaches added in 2022-2027. Cardiopulmonary exercise testing, two-dimensional Doppler echocardiography, and carotid-femoral pulse wave velocity will be used to quantify functional and structural changes central to heart failure.
Dr. Nathan commented that, although enough cardiovascular events were available in EDIC by 2006 to demonstrate a significant 58% reduction in the intensive therapy group, “now we can start looking at the aging heart. We have a bunch of great cardiologists working with us who will be guiding us on measuring everything.”
Fatty liver disease in the setting of increasing adiposity will also be investigated using transient elastography (FibroScan) and the Fibrosis-4 index, a quantification of liver enzymes and platelet count.
Dr. Nathan noted that the study participants have had “this kind of funny metabolic milieu in their liver for decades. They don’t make insulin in their pancreas, and therefore, the insulin they get is peripheral and then it goes to their liver. Well, what does that do to them?”
Participants will also complete three symptom questionnaires assessing obstructive sleep apnea, aimed at guiding future sleep studies in those found to be at high risk, Dr. Braffett said.
DCCT/EDIC over 40 years: ‘Incredibly complete picture’
As of 2023, the DCCT/EDIC participants have been studied for longer than 60% of their lifespans and for over 80% of their diabetes duration, Dr. Braffett noted.
During the EDIC 2017-2022 cycle, Dr. Braffett and other speakers summarized, prior EDIC efforts had focused on aspects of cognitive function, physical function, and cheiroarthropathy.
Other DCCT/EDIC studies examined the relationship of A1c and diabetes duration in cardiovascular disease risk, the association of microvascular complications with the risk of cardiovascular disease beyond traditional risk factors, and the risk of severe hypoglycemia over the first 30 years of DCCT/EDIC follow-up.
Moreover, the longitudinal eye and kidney assessments over the 40 years have informed screening guidelines for retinopathy and urinary albumin.
Dr. Nathan said: “Today, the number with horrible complications is very few, but we haven’t erased complications entirely. ... We have this incredibly complete picture of type 1 diabetes that allows us to explore everything. We welcome people to come to us with ideas. That’s the value of this research.”
Dr. Nathan, Ms. Lorenzi, and Dr. Braffett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN DIEGO –
New funding for 2022-2027 for the DCCT long-term observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) will go toward investigating aspects of type 1 diabetes that are associated with aging and are also common in type 2 diabetes, including cardiovascular disease, fatty liver disease, and sleep apnea.
The original randomized DCCT clinical trial results, published in 1993 in the New England Journal of Medicine, proved that early intensive glycemic control was the key to preventing or slowing the progression of long-term eye, kidney, and nerve complications of type 1 diabetes. Subsequently, EDIC has yielded many more major findings including that early tight glycemic control also reduces cardiovascular risk and prolongs survival in type 1 diabetes.
And although the phenomenon of metabolic memory initially seen in EDIC means that early glycemic control is important, subsequent EDIC data also have suggested that it is never too late to initiate intensive glycemic control, speakers emphasized during a special symposium commemorating 40 years since the start of DCCT, held during the annual scientific sessions of the American Diabetes Association. As with the 30-year DCCT/EDIC commemorative symposium held in 2013, local study participants were in the audience and were acknowledged with long applause.
Together, DCCT and EDIC – both funded by the National Institutes of Health at 27 sites in the United States and Canada – have changed the standard of care for people with type 1 diabetes and continue to inform clinical practice. Prior to the DCCT, between 1930 and 1970, about a third of people with type 1 diabetes developed vision loss and one in five experienced kidney failure and/or myocardial infarction. Stroke and amputation were also common, DCCT/EDIC chair David M. Nathan, MD, said while introducing the symposium.
“All of the advances in care of type 1 diabetes have developed because this study demonstrated that it was important – continuous glucose monitoring (CGM), new insulins, better [insulin] pumps. ... I think the most profound finding is that mortality in our intensively treated cohort is the same as in the general population. That says it all,” Dr. Nathan said in an interview.
And now, “what we still have yet to contribute is what happens to type 1 diabetes as people get older,” added Dr. Nathan, a professor of medicine at Harvard Medical School and director of the Diabetes Center at Massachusetts General Hospital, both in Boston.
‘Something that heretofore none of us could have imagined’
The 1,441 DCCT participants had a mean age of 27 years at baseline in 1983, when they were randomized to intensive insulin therapy or usual care. The 1,375 participants (96%) who continued into EDIC in 1994 were an average of 35 years old at that point, when the usual care group was taught intensive glycemic management and all participants returned to their personal health care teams. The 1,075 participants in EDIC today are an average age of 63 years.
Only 11 participants had died at the start of EDIC, and just 250 (17%) have died as of 2023, said study coordinator cochair Gayle Lorenzi, RN, who is a certified diabetes care and education specialist at the University of California, San Diego.
“DCCT/EDIC because of its longevity represents a unique opportunity to explore aging in long duration of type 1 diabetes, something that heretofore none of us could have imagined, especially for those of you in the audience who started your careers in the 70s and 80s,” Ms. Lorenzi commented.
About 36% of the cohort now has overweight and 40% have obesity, mirroring the general population. And they now have a mean hemoglobin A1c of 7.3%.
According to Barbara H. Braffett, PhD, co–principal investigator at the DCCT/EDIC data coordinating center: “The EDIC study is now shifting its focus during the next 5 years to understand the clinical course of type 1 diabetes in the setting of advancing duration and age, as well as increasing adiposity, which has progressively affected individuals with type 1 diabetes and has potential long-term adverse consequences.”
Dr. Braffett outlined the new study approaches added in 2022-2027. Cardiopulmonary exercise testing, two-dimensional Doppler echocardiography, and carotid-femoral pulse wave velocity will be used to quantify functional and structural changes central to heart failure.
Dr. Nathan commented that, although enough cardiovascular events were available in EDIC by 2006 to demonstrate a significant 58% reduction in the intensive therapy group, “now we can start looking at the aging heart. We have a bunch of great cardiologists working with us who will be guiding us on measuring everything.”
Fatty liver disease in the setting of increasing adiposity will also be investigated using transient elastography (FibroScan) and the Fibrosis-4 index, a quantification of liver enzymes and platelet count.
Dr. Nathan noted that the study participants have had “this kind of funny metabolic milieu in their liver for decades. They don’t make insulin in their pancreas, and therefore, the insulin they get is peripheral and then it goes to their liver. Well, what does that do to them?”
Participants will also complete three symptom questionnaires assessing obstructive sleep apnea, aimed at guiding future sleep studies in those found to be at high risk, Dr. Braffett said.
DCCT/EDIC over 40 years: ‘Incredibly complete picture’
As of 2023, the DCCT/EDIC participants have been studied for longer than 60% of their lifespans and for over 80% of their diabetes duration, Dr. Braffett noted.
During the EDIC 2017-2022 cycle, Dr. Braffett and other speakers summarized, prior EDIC efforts had focused on aspects of cognitive function, physical function, and cheiroarthropathy.
Other DCCT/EDIC studies examined the relationship of A1c and diabetes duration in cardiovascular disease risk, the association of microvascular complications with the risk of cardiovascular disease beyond traditional risk factors, and the risk of severe hypoglycemia over the first 30 years of DCCT/EDIC follow-up.
Moreover, the longitudinal eye and kidney assessments over the 40 years have informed screening guidelines for retinopathy and urinary albumin.
Dr. Nathan said: “Today, the number with horrible complications is very few, but we haven’t erased complications entirely. ... We have this incredibly complete picture of type 1 diabetes that allows us to explore everything. We welcome people to come to us with ideas. That’s the value of this research.”
Dr. Nathan, Ms. Lorenzi, and Dr. Braffett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN DIEGO –
New funding for 2022-2027 for the DCCT long-term observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) will go toward investigating aspects of type 1 diabetes that are associated with aging and are also common in type 2 diabetes, including cardiovascular disease, fatty liver disease, and sleep apnea.
The original randomized DCCT clinical trial results, published in 1993 in the New England Journal of Medicine, proved that early intensive glycemic control was the key to preventing or slowing the progression of long-term eye, kidney, and nerve complications of type 1 diabetes. Subsequently, EDIC has yielded many more major findings including that early tight glycemic control also reduces cardiovascular risk and prolongs survival in type 1 diabetes.
And although the phenomenon of metabolic memory initially seen in EDIC means that early glycemic control is important, subsequent EDIC data also have suggested that it is never too late to initiate intensive glycemic control, speakers emphasized during a special symposium commemorating 40 years since the start of DCCT, held during the annual scientific sessions of the American Diabetes Association. As with the 30-year DCCT/EDIC commemorative symposium held in 2013, local study participants were in the audience and were acknowledged with long applause.
Together, DCCT and EDIC – both funded by the National Institutes of Health at 27 sites in the United States and Canada – have changed the standard of care for people with type 1 diabetes and continue to inform clinical practice. Prior to the DCCT, between 1930 and 1970, about a third of people with type 1 diabetes developed vision loss and one in five experienced kidney failure and/or myocardial infarction. Stroke and amputation were also common, DCCT/EDIC chair David M. Nathan, MD, said while introducing the symposium.
“All of the advances in care of type 1 diabetes have developed because this study demonstrated that it was important – continuous glucose monitoring (CGM), new insulins, better [insulin] pumps. ... I think the most profound finding is that mortality in our intensively treated cohort is the same as in the general population. That says it all,” Dr. Nathan said in an interview.
And now, “what we still have yet to contribute is what happens to type 1 diabetes as people get older,” added Dr. Nathan, a professor of medicine at Harvard Medical School and director of the Diabetes Center at Massachusetts General Hospital, both in Boston.
‘Something that heretofore none of us could have imagined’
The 1,441 DCCT participants had a mean age of 27 years at baseline in 1983, when they were randomized to intensive insulin therapy or usual care. The 1,375 participants (96%) who continued into EDIC in 1994 were an average of 35 years old at that point, when the usual care group was taught intensive glycemic management and all participants returned to their personal health care teams. The 1,075 participants in EDIC today are an average age of 63 years.
Only 11 participants had died at the start of EDIC, and just 250 (17%) have died as of 2023, said study coordinator cochair Gayle Lorenzi, RN, who is a certified diabetes care and education specialist at the University of California, San Diego.
“DCCT/EDIC because of its longevity represents a unique opportunity to explore aging in long duration of type 1 diabetes, something that heretofore none of us could have imagined, especially for those of you in the audience who started your careers in the 70s and 80s,” Ms. Lorenzi commented.
About 36% of the cohort now has overweight and 40% have obesity, mirroring the general population. And they now have a mean hemoglobin A1c of 7.3%.
According to Barbara H. Braffett, PhD, co–principal investigator at the DCCT/EDIC data coordinating center: “The EDIC study is now shifting its focus during the next 5 years to understand the clinical course of type 1 diabetes in the setting of advancing duration and age, as well as increasing adiposity, which has progressively affected individuals with type 1 diabetes and has potential long-term adverse consequences.”
Dr. Braffett outlined the new study approaches added in 2022-2027. Cardiopulmonary exercise testing, two-dimensional Doppler echocardiography, and carotid-femoral pulse wave velocity will be used to quantify functional and structural changes central to heart failure.
Dr. Nathan commented that, although enough cardiovascular events were available in EDIC by 2006 to demonstrate a significant 58% reduction in the intensive therapy group, “now we can start looking at the aging heart. We have a bunch of great cardiologists working with us who will be guiding us on measuring everything.”
Fatty liver disease in the setting of increasing adiposity will also be investigated using transient elastography (FibroScan) and the Fibrosis-4 index, a quantification of liver enzymes and platelet count.
Dr. Nathan noted that the study participants have had “this kind of funny metabolic milieu in their liver for decades. They don’t make insulin in their pancreas, and therefore, the insulin they get is peripheral and then it goes to their liver. Well, what does that do to them?”
Participants will also complete three symptom questionnaires assessing obstructive sleep apnea, aimed at guiding future sleep studies in those found to be at high risk, Dr. Braffett said.
DCCT/EDIC over 40 years: ‘Incredibly complete picture’
As of 2023, the DCCT/EDIC participants have been studied for longer than 60% of their lifespans and for over 80% of their diabetes duration, Dr. Braffett noted.
During the EDIC 2017-2022 cycle, Dr. Braffett and other speakers summarized, prior EDIC efforts had focused on aspects of cognitive function, physical function, and cheiroarthropathy.
Other DCCT/EDIC studies examined the relationship of A1c and diabetes duration in cardiovascular disease risk, the association of microvascular complications with the risk of cardiovascular disease beyond traditional risk factors, and the risk of severe hypoglycemia over the first 30 years of DCCT/EDIC follow-up.
Moreover, the longitudinal eye and kidney assessments over the 40 years have informed screening guidelines for retinopathy and urinary albumin.
Dr. Nathan said: “Today, the number with horrible complications is very few, but we haven’t erased complications entirely. ... We have this incredibly complete picture of type 1 diabetes that allows us to explore everything. We welcome people to come to us with ideas. That’s the value of this research.”
Dr. Nathan, Ms. Lorenzi, and Dr. Braffett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ADA 2023
Education before Ramadan key to safe fasting with diabetes
SAN DIEGO – An assessment of people with diabetes before Ramadan is vital so they can learn whether it is safe for them to fast, and if it is, how to do so without jeopardizing their health.
“With correct advice and support” from knowledgeable health care professionals “most people with type 2 diabetes can fast safely during Ramadan,” Mohamed Hassanein, MBChB, said at the annual scientific sessions of the American Diabetes Association.
One of the most authoritative guidelines on how people with diabetes can safely fast during Ramadan has come from a collaboration between the International Diabetes Federation and the Diabetes & Ramadan International Alliance, an organization chaired by Dr. Hassanein. The groups issued a revised practical guide in 2021 for Ramadan fasting for people with diabetes, an update of the first edition released in 2016. Dr. Hassanein was lead author of the 2016 guidelines and edited the 2021 revision.
The 2021 guidelines also led to an update of a risk stratification app available for free from the DAR. The app provides risk stratification for people with diabetes and helps them access educational material to guide them through their fasts.
Although the latest guidelines address fasting for people with type 1 or type 2 diabetes, far more people with type 2 diabetes are at risk from fasting, and not only because of the higher prevalence of type 2 diabetes.
Results from a global survey of Muslims with diabetes in 2020 showed that 30% of those with type 1 diabetes did not do any fasting during Ramadan, but the percentage of those abstaining from fasting dropped to 16% among Muslims with type 2 diabetes, Dr. Hassanein explained. (Survey results in 2013 from about 38,000 Muslims in 39 countries showed a median of 7% of all adults did no fasting during Ramadan.)
Risk assessment by app
Currently, the DAR app is available in Arabic, English, French, and Urdu (the primary language of Pakistan), with more languages being added soon, said Dr. Hassanein, an endocrinologist at Dubai Hospital and professor at Mohammed Bin-Rashid University of Medicine & Health Sciences in Dubai, United Arab Emirates.
The app and screening protocol divides people with diabetes into low-, moderate-, and high-risk subgroups, and those at high risk are advised to refrain from fasting.
But the many other people with diabetes who potentially could fast still face risks for hypoglycemia, hyperglycemia (from overindulgent break-fast meals), diabetic ketoacidosis, dehydration, and thrombosis. Individual risk for these adverse events depends on many factors, including age, duration of diabetes, diabetes type, treatments received, history of hypoglycemia, and diabetes complications.
Dr. Hassanein and colleagues documented the high rate of complications from fasting in a 2020 survey of more than 5,800 Muslims with type 2 diabetes from 20 countries. The results showed that 72% of survey participants had to interrupt their 30 days of daily fasting for at least 1 day because of a diabetes-related event, and an additional 28% had diabetes-triggered interruptions that totaled more than 7 days. About 7% required hospitalization or an emergency department visit, and 16% developed at least one episode of daytime hypoglycemia.
Endorsement from Islamic clerics
The recommended risk assessment, and resulting exemptions from fasting, have been endorsed by the Mofty of Egypt, a group of religious scholars who issue legal opinions interpreting Islamic law.
The Mofty agreed that fasting should be interrupted for cases of hypoglycemia with blood glucose less than 70 mg/dL, hyperglycemia with blood glucose greater than 300 mg/dL, symptoms of hypo- or hyperglycemia, or symptoms of acute illness. The Mofty also endorsed that although fasting is obligatory for low-risk adults with diabetes and preferred for those with moderate-risk diabetes, the latter group may consider not fasting out of concern for their safety or to take prescribed medications. People at high risk were deemed by the Mofty as individuals who should not fast because of the potential for harm.
Other notable 2020 survey findings included pre-Ramadan education being received by just 43% of the respondents, and no self-monitoring of blood glucose performed by about a quarter of the respondents.
The 2021 guidelines also include treatment recommendations, such as avoiding older, longer-acting sulfonylurea agents in people with type 2 diabetes. And having people achieve stable, guideline-directed dosages of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists before Ramadan starts, rather than trying to initiate these agents during Ramadan. The guidelines also recommend reducing usual insulin doses when fasting during Ramadan.
Despite summarizing findings from several observational studies and surveys, research to date on how to optimize the safety of diabetes management during Ramadan fasting “is all very basic,” Dr. Hassanein said in an interview.
“We need more randomized clinical trials. We need more [data and evidence] for every single aspect” of management, he added.
The 2021 Diabetes and Ramadan Practical Guidelines were supported by an educational grant from Sanofi and Servier. Dr. Hassanein has reported being a speaker on behalf of Abbott, AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, and Servier.
A version of this article first appeared on Medscape.com.
SAN DIEGO – An assessment of people with diabetes before Ramadan is vital so they can learn whether it is safe for them to fast, and if it is, how to do so without jeopardizing their health.
“With correct advice and support” from knowledgeable health care professionals “most people with type 2 diabetes can fast safely during Ramadan,” Mohamed Hassanein, MBChB, said at the annual scientific sessions of the American Diabetes Association.
One of the most authoritative guidelines on how people with diabetes can safely fast during Ramadan has come from a collaboration between the International Diabetes Federation and the Diabetes & Ramadan International Alliance, an organization chaired by Dr. Hassanein. The groups issued a revised practical guide in 2021 for Ramadan fasting for people with diabetes, an update of the first edition released in 2016. Dr. Hassanein was lead author of the 2016 guidelines and edited the 2021 revision.
The 2021 guidelines also led to an update of a risk stratification app available for free from the DAR. The app provides risk stratification for people with diabetes and helps them access educational material to guide them through their fasts.
Although the latest guidelines address fasting for people with type 1 or type 2 diabetes, far more people with type 2 diabetes are at risk from fasting, and not only because of the higher prevalence of type 2 diabetes.
Results from a global survey of Muslims with diabetes in 2020 showed that 30% of those with type 1 diabetes did not do any fasting during Ramadan, but the percentage of those abstaining from fasting dropped to 16% among Muslims with type 2 diabetes, Dr. Hassanein explained. (Survey results in 2013 from about 38,000 Muslims in 39 countries showed a median of 7% of all adults did no fasting during Ramadan.)
Risk assessment by app
Currently, the DAR app is available in Arabic, English, French, and Urdu (the primary language of Pakistan), with more languages being added soon, said Dr. Hassanein, an endocrinologist at Dubai Hospital and professor at Mohammed Bin-Rashid University of Medicine & Health Sciences in Dubai, United Arab Emirates.
The app and screening protocol divides people with diabetes into low-, moderate-, and high-risk subgroups, and those at high risk are advised to refrain from fasting.
But the many other people with diabetes who potentially could fast still face risks for hypoglycemia, hyperglycemia (from overindulgent break-fast meals), diabetic ketoacidosis, dehydration, and thrombosis. Individual risk for these adverse events depends on many factors, including age, duration of diabetes, diabetes type, treatments received, history of hypoglycemia, and diabetes complications.
Dr. Hassanein and colleagues documented the high rate of complications from fasting in a 2020 survey of more than 5,800 Muslims with type 2 diabetes from 20 countries. The results showed that 72% of survey participants had to interrupt their 30 days of daily fasting for at least 1 day because of a diabetes-related event, and an additional 28% had diabetes-triggered interruptions that totaled more than 7 days. About 7% required hospitalization or an emergency department visit, and 16% developed at least one episode of daytime hypoglycemia.
Endorsement from Islamic clerics
The recommended risk assessment, and resulting exemptions from fasting, have been endorsed by the Mofty of Egypt, a group of religious scholars who issue legal opinions interpreting Islamic law.
The Mofty agreed that fasting should be interrupted for cases of hypoglycemia with blood glucose less than 70 mg/dL, hyperglycemia with blood glucose greater than 300 mg/dL, symptoms of hypo- or hyperglycemia, or symptoms of acute illness. The Mofty also endorsed that although fasting is obligatory for low-risk adults with diabetes and preferred for those with moderate-risk diabetes, the latter group may consider not fasting out of concern for their safety or to take prescribed medications. People at high risk were deemed by the Mofty as individuals who should not fast because of the potential for harm.
Other notable 2020 survey findings included pre-Ramadan education being received by just 43% of the respondents, and no self-monitoring of blood glucose performed by about a quarter of the respondents.
The 2021 guidelines also include treatment recommendations, such as avoiding older, longer-acting sulfonylurea agents in people with type 2 diabetes. And having people achieve stable, guideline-directed dosages of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists before Ramadan starts, rather than trying to initiate these agents during Ramadan. The guidelines also recommend reducing usual insulin doses when fasting during Ramadan.
Despite summarizing findings from several observational studies and surveys, research to date on how to optimize the safety of diabetes management during Ramadan fasting “is all very basic,” Dr. Hassanein said in an interview.
“We need more randomized clinical trials. We need more [data and evidence] for every single aspect” of management, he added.
The 2021 Diabetes and Ramadan Practical Guidelines were supported by an educational grant from Sanofi and Servier. Dr. Hassanein has reported being a speaker on behalf of Abbott, AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, and Servier.
A version of this article first appeared on Medscape.com.
SAN DIEGO – An assessment of people with diabetes before Ramadan is vital so they can learn whether it is safe for them to fast, and if it is, how to do so without jeopardizing their health.
“With correct advice and support” from knowledgeable health care professionals “most people with type 2 diabetes can fast safely during Ramadan,” Mohamed Hassanein, MBChB, said at the annual scientific sessions of the American Diabetes Association.
One of the most authoritative guidelines on how people with diabetes can safely fast during Ramadan has come from a collaboration between the International Diabetes Federation and the Diabetes & Ramadan International Alliance, an organization chaired by Dr. Hassanein. The groups issued a revised practical guide in 2021 for Ramadan fasting for people with diabetes, an update of the first edition released in 2016. Dr. Hassanein was lead author of the 2016 guidelines and edited the 2021 revision.
The 2021 guidelines also led to an update of a risk stratification app available for free from the DAR. The app provides risk stratification for people with diabetes and helps them access educational material to guide them through their fasts.
Although the latest guidelines address fasting for people with type 1 or type 2 diabetes, far more people with type 2 diabetes are at risk from fasting, and not only because of the higher prevalence of type 2 diabetes.
Results from a global survey of Muslims with diabetes in 2020 showed that 30% of those with type 1 diabetes did not do any fasting during Ramadan, but the percentage of those abstaining from fasting dropped to 16% among Muslims with type 2 diabetes, Dr. Hassanein explained. (Survey results in 2013 from about 38,000 Muslims in 39 countries showed a median of 7% of all adults did no fasting during Ramadan.)
Risk assessment by app
Currently, the DAR app is available in Arabic, English, French, and Urdu (the primary language of Pakistan), with more languages being added soon, said Dr. Hassanein, an endocrinologist at Dubai Hospital and professor at Mohammed Bin-Rashid University of Medicine & Health Sciences in Dubai, United Arab Emirates.
The app and screening protocol divides people with diabetes into low-, moderate-, and high-risk subgroups, and those at high risk are advised to refrain from fasting.
But the many other people with diabetes who potentially could fast still face risks for hypoglycemia, hyperglycemia (from overindulgent break-fast meals), diabetic ketoacidosis, dehydration, and thrombosis. Individual risk for these adverse events depends on many factors, including age, duration of diabetes, diabetes type, treatments received, history of hypoglycemia, and diabetes complications.
Dr. Hassanein and colleagues documented the high rate of complications from fasting in a 2020 survey of more than 5,800 Muslims with type 2 diabetes from 20 countries. The results showed that 72% of survey participants had to interrupt their 30 days of daily fasting for at least 1 day because of a diabetes-related event, and an additional 28% had diabetes-triggered interruptions that totaled more than 7 days. About 7% required hospitalization or an emergency department visit, and 16% developed at least one episode of daytime hypoglycemia.
Endorsement from Islamic clerics
The recommended risk assessment, and resulting exemptions from fasting, have been endorsed by the Mofty of Egypt, a group of religious scholars who issue legal opinions interpreting Islamic law.
The Mofty agreed that fasting should be interrupted for cases of hypoglycemia with blood glucose less than 70 mg/dL, hyperglycemia with blood glucose greater than 300 mg/dL, symptoms of hypo- or hyperglycemia, or symptoms of acute illness. The Mofty also endorsed that although fasting is obligatory for low-risk adults with diabetes and preferred for those with moderate-risk diabetes, the latter group may consider not fasting out of concern for their safety or to take prescribed medications. People at high risk were deemed by the Mofty as individuals who should not fast because of the potential for harm.
Other notable 2020 survey findings included pre-Ramadan education being received by just 43% of the respondents, and no self-monitoring of blood glucose performed by about a quarter of the respondents.
The 2021 guidelines also include treatment recommendations, such as avoiding older, longer-acting sulfonylurea agents in people with type 2 diabetes. And having people achieve stable, guideline-directed dosages of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists before Ramadan starts, rather than trying to initiate these agents during Ramadan. The guidelines also recommend reducing usual insulin doses when fasting during Ramadan.
Despite summarizing findings from several observational studies and surveys, research to date on how to optimize the safety of diabetes management during Ramadan fasting “is all very basic,” Dr. Hassanein said in an interview.
“We need more randomized clinical trials. We need more [data and evidence] for every single aspect” of management, he added.
The 2021 Diabetes and Ramadan Practical Guidelines were supported by an educational grant from Sanofi and Servier. Dr. Hassanein has reported being a speaker on behalf of Abbott, AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, and Servier.
A version of this article first appeared on Medscape.com.
AT ADA 2023
COORDINATE-Diabetes: A ‘wake-up call’ for many specialties
SAN DIEGO – at the annual scientific sessions of the American Diabetes Association.
A symposium there focused on the recent randomized, controlled COORDINATE-Diabetes trial, which investigated a multipronged educational intervention in 43 U.S. cardiology clinics aimed at improving prescribing of guideline-recommended treatments for people with both type 2 diabetes and cardiovascular disease. Compared with clinics that were randomly assigned to offer usual care, the intervention significantly increased recommended prescribing of high-intensity statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ARBs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors and/or glucagonlike peptide 1 receptor agonists (GLP-1 agonists).
COORDINATE-Diabetes was aimed at cardiologists, who typically see these patients more often than do endocrinologists. However, the results are relevant to all health care providers involved in the care of those with type 2 diabetes, speakers argued at the ADA symposium.
“This is a cardiology study. I think it’s safe to say that not too many of you in the room are cardiologists. So why would you care about the results of the COORDINATE study?” said Ildiko Lingvay, MD, of the University of Texas Southwestern Medical Center, Dallas.
Dr. Lingvay went on to outline reasons that the COORDINATE findings apply to endocrinologists and primary care clinicians, as well as cardiologists. For one, a study from her institution that was presented at a recent internal medicine meeting showed that, among more than 10,000 patients with type 2 diabetes and cardiovascular disease, heart failure, and/or chronic kidney disease, the proportion of patients who were prescribed the appropriate guideline-indicated medications was 20.1% for those seen in primary care, 24.8% in endocrinology, 20.3% in cardiology, and 18.3% in nephrology.
“So, we [endocrinologists are] not that much better [than other specialties]” at prescribing, she noted.
Mikhail N. Kosiborod, MD, in independent commentary called the COORDINATE trial and other similar initiatives “the beginning of care transformation.”
The COORDINATE-Diabetes results were originally presented in March at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published in JAMA.
‘They’ve shown we can do better’
Asked to comment, Robert H. Eckel, MD, said in an interview, “I look at COORDINATE as a wake-up call to the need for multispecialty approaches to people with type 2 diabetes and cardiovascular disease. ... I think it’s a step in the door.”
Dr. Eckel, who has long advocated for a new “cardiometabolic” physician subspecialty, noted that COORDINATE-Diabetes “stopped short of training health care providers in the science and medicine of cardio-renal-metabolic disease.”
Nonetheless, regarding the efforts toward a more coordinated system of care, Dr. Eckel said, “I support the concept, unequivocally.” He is associated with the division of endocrinology, metabolism, and diabetes, University of Colorado at Denver, Aurora.
But the cost-effectiveness of the intervention “requires time to assess,” he added. “We don’t know anything yet other than [that] managing drug administration to meet goals that relate to outcomes in people with diabetes can be accomplished. They’ve shown that we can do better.”
Why should you care about a cardiology study?
In COORDINATE-Diabetes, 20 of the centers were randomly assigned to provide five interventions: assess local barriers, develop care pathways, coordinate care, educate clinicians, report data back to the clinics, and provide tools for the 459 participants. The other 23 clinics, with 590 participants, were randomly assigned to provide usual care per practice guidelines.
The primary outcome was the proportion of participants that prescribed all three groups of the recommended therapies at 6-12 months after enrollment; 37.9% prescribed the intervention, and 14.5% provided usual care, a significant 23% difference (P < .001). The rate of prescriptions of each of the three individual drug groups was also significantly higher with the intervention. No differences were seen in cardiovascular risk factors or outcomes.
Dr. Lingvay pointed out that the interventions tested in COORDINATE – such as fact sheets and medication passports for patients, system audits and feedback, and provider grand rounds – can be extrapolated to any specialist setting.
She added that the long-held model of team-based care means that “everyone involved in the care of these patients is responsible for ensuring best practices are followed.” Part of that, she said, is helping other specialists prescribe the same medications and communicate across the team.
For all specialists, she recommends using the resources available on the COORDINATE website.
‘It’s not a silver bullet; additional solutions are needed’
In his commentary, Dr. Kosiborod, executive director of the Cardiometabolic Center Alliance, noted, “The treatments studied in COORDINATE represent the biggest advances in a generation when it comes to improving outcomes in this population. ... We’re living in a renaissance age with the number of tools we have available. ... It’s getting better every day.”
Moreover, all the relevant professional society guidelines now recommend GLP-1 agonists and SGLT2 inhibitors. “And yet, when we look, less than 1 in 10 patients with type 2 diabetes and atherosclerotic cardiovascular disease are getting appropriate recommended care. One of the lessons of COORDINATE is that this needs to change if we’re really going to improve our patients’ lives.”
The barriers aren’t simply financial, Dr. Kosiborod said. He pointed to two studies that show that even reducing out-of-pocket costs resulted in only modest increases in adherence.
Educational gaps on the part of both clinicians and patients also factor in, as do misaligned incentives.
“Clinicians get paid for how many things they do, not necessarily how well they do them. Everyone wants to do the right thing, but ultimately, incentives do matter,” he emphasized.
While the COORDINATE-Diabetes interventions addressed several of the barriers, two-thirds of the participants still did not receive optimal therapy.
“It’s not a silver bullet. ... Additional solutions are needed,” Dr. Kosiborod observed.
Transformation occurs ‘when the status quo is no longer acceptable’
Enter his institution, the Cardiometabolic Center Alliance, part of Saint Luke’s Mid-America Heart Institute. The nonprofit system, which currently has 16 subscribing clinics around the country, offers patient-centered “team-based, coordinated, comprehensive care” for people with both type 2 diabetes and cardiovascular disease.
The model is led by preventive cardiology in collaboration with endocrinology and primary care. Support staff includes advance practice providers, nurse navigators, certified diabetes educators, dietitians, and pharmacists. Individualized treatment plans aim for “aggressive secondary risk reduction,” Dr. Kosiborod noted.
Six-month data from the Cardiometabolic Center Alliance show an increase from 28.2% at baseline to 67.1% (P < .0001) in prescribing of a four-agent guideline-directed medical therapy “bundle,” including the three from COORDINATE-Diabetes plus an antiplatelet or anticoagulant agent. Dr. Kosiborod presented these data during the ADA meeting in a poster.
Remaining questions involve sustainability, scalability, and system transformation, which require buy-in from multiple stakeholders, he noted.
He contends that it can be done. A prior example of “rapid and lasting care transformation” occurred in November 2006 with the launch of the “Door to Balloon (D2B) Alliance for Quality,” which dramatically increased the proportion of patients who received primary angioplasty within 90 minutes at hospitals around the United States. From January 2005 to September 2010, those proportions rose from 27.3% to 70.4%.
“Patients were coming into the emergency department with myocardial infarctions and waiting for hours before the interventional cardiologist came. The community said we needed a nationwide quality improvement initiative. ... Almost every hospital in the country changed their systems of care. It was a huge national effort. ... When we no longer consider the status quo acceptable, we can actually make something very special happen very quickly.”
After the session, Dr. Kosiborod said in an interview that the Cardiometabolic Center Alliance is now gathering data to make the financial case for the approach.
“We’re trying to develop a model that tells the admins which patients will save money, because, of course, if you can create a financial incentive, it only makes it go faster. ... We want to synchronize it in the best way possible.”
Dr. Lingvay has receiving nonfinancial support and grants from Novo Nordisk, personal fees or nonfinancial support from Sanofi, Lilly, Boehringer Ingelheim, Merck/Pfizer, Mylan, AstraZeneca, Johnson & Johnson, Intercept, Target Pharma, Zealand, Shionogi, Carmot, Structure, Bayer, Mediflix, WebMD, GI Dynamics, Intarcia Therapeutics, Mannkind, Novartis, Structure Therapeutics, and Valeritas. Dr. Kosiborod is a consultant for Alnylam Pharmaceuticals, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, ESPERION Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Novo Nordisk, Pharmacosmos, Pfizer, Sanofi, Vifor Pharma Management, and Youngene Therapeutics. He also receives research support from AstraZeneca and Boehringer Ingelheim. Dr. Eckel serves on consulting/advisory boards for Amgen, Arrowhead, Better, Ionis, Kowa, Lexicon, Novo Nordisk, Precision BioSciences, The Healthy Aging Company, Tolmar, and Weight Watchers.
A version of this article first appeared on Medscape.com.
SAN DIEGO – at the annual scientific sessions of the American Diabetes Association.
A symposium there focused on the recent randomized, controlled COORDINATE-Diabetes trial, which investigated a multipronged educational intervention in 43 U.S. cardiology clinics aimed at improving prescribing of guideline-recommended treatments for people with both type 2 diabetes and cardiovascular disease. Compared with clinics that were randomly assigned to offer usual care, the intervention significantly increased recommended prescribing of high-intensity statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ARBs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors and/or glucagonlike peptide 1 receptor agonists (GLP-1 agonists).
COORDINATE-Diabetes was aimed at cardiologists, who typically see these patients more often than do endocrinologists. However, the results are relevant to all health care providers involved in the care of those with type 2 diabetes, speakers argued at the ADA symposium.
“This is a cardiology study. I think it’s safe to say that not too many of you in the room are cardiologists. So why would you care about the results of the COORDINATE study?” said Ildiko Lingvay, MD, of the University of Texas Southwestern Medical Center, Dallas.
Dr. Lingvay went on to outline reasons that the COORDINATE findings apply to endocrinologists and primary care clinicians, as well as cardiologists. For one, a study from her institution that was presented at a recent internal medicine meeting showed that, among more than 10,000 patients with type 2 diabetes and cardiovascular disease, heart failure, and/or chronic kidney disease, the proportion of patients who were prescribed the appropriate guideline-indicated medications was 20.1% for those seen in primary care, 24.8% in endocrinology, 20.3% in cardiology, and 18.3% in nephrology.
“So, we [endocrinologists are] not that much better [than other specialties]” at prescribing, she noted.
Mikhail N. Kosiborod, MD, in independent commentary called the COORDINATE trial and other similar initiatives “the beginning of care transformation.”
The COORDINATE-Diabetes results were originally presented in March at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published in JAMA.
‘They’ve shown we can do better’
Asked to comment, Robert H. Eckel, MD, said in an interview, “I look at COORDINATE as a wake-up call to the need for multispecialty approaches to people with type 2 diabetes and cardiovascular disease. ... I think it’s a step in the door.”
Dr. Eckel, who has long advocated for a new “cardiometabolic” physician subspecialty, noted that COORDINATE-Diabetes “stopped short of training health care providers in the science and medicine of cardio-renal-metabolic disease.”
Nonetheless, regarding the efforts toward a more coordinated system of care, Dr. Eckel said, “I support the concept, unequivocally.” He is associated with the division of endocrinology, metabolism, and diabetes, University of Colorado at Denver, Aurora.
But the cost-effectiveness of the intervention “requires time to assess,” he added. “We don’t know anything yet other than [that] managing drug administration to meet goals that relate to outcomes in people with diabetes can be accomplished. They’ve shown that we can do better.”
Why should you care about a cardiology study?
In COORDINATE-Diabetes, 20 of the centers were randomly assigned to provide five interventions: assess local barriers, develop care pathways, coordinate care, educate clinicians, report data back to the clinics, and provide tools for the 459 participants. The other 23 clinics, with 590 participants, were randomly assigned to provide usual care per practice guidelines.
The primary outcome was the proportion of participants that prescribed all three groups of the recommended therapies at 6-12 months after enrollment; 37.9% prescribed the intervention, and 14.5% provided usual care, a significant 23% difference (P < .001). The rate of prescriptions of each of the three individual drug groups was also significantly higher with the intervention. No differences were seen in cardiovascular risk factors or outcomes.
Dr. Lingvay pointed out that the interventions tested in COORDINATE – such as fact sheets and medication passports for patients, system audits and feedback, and provider grand rounds – can be extrapolated to any specialist setting.
She added that the long-held model of team-based care means that “everyone involved in the care of these patients is responsible for ensuring best practices are followed.” Part of that, she said, is helping other specialists prescribe the same medications and communicate across the team.
For all specialists, she recommends using the resources available on the COORDINATE website.
‘It’s not a silver bullet; additional solutions are needed’
In his commentary, Dr. Kosiborod, executive director of the Cardiometabolic Center Alliance, noted, “The treatments studied in COORDINATE represent the biggest advances in a generation when it comes to improving outcomes in this population. ... We’re living in a renaissance age with the number of tools we have available. ... It’s getting better every day.”
Moreover, all the relevant professional society guidelines now recommend GLP-1 agonists and SGLT2 inhibitors. “And yet, when we look, less than 1 in 10 patients with type 2 diabetes and atherosclerotic cardiovascular disease are getting appropriate recommended care. One of the lessons of COORDINATE is that this needs to change if we’re really going to improve our patients’ lives.”
The barriers aren’t simply financial, Dr. Kosiborod said. He pointed to two studies that show that even reducing out-of-pocket costs resulted in only modest increases in adherence.
Educational gaps on the part of both clinicians and patients also factor in, as do misaligned incentives.
“Clinicians get paid for how many things they do, not necessarily how well they do them. Everyone wants to do the right thing, but ultimately, incentives do matter,” he emphasized.
While the COORDINATE-Diabetes interventions addressed several of the barriers, two-thirds of the participants still did not receive optimal therapy.
“It’s not a silver bullet. ... Additional solutions are needed,” Dr. Kosiborod observed.
Transformation occurs ‘when the status quo is no longer acceptable’
Enter his institution, the Cardiometabolic Center Alliance, part of Saint Luke’s Mid-America Heart Institute. The nonprofit system, which currently has 16 subscribing clinics around the country, offers patient-centered “team-based, coordinated, comprehensive care” for people with both type 2 diabetes and cardiovascular disease.
The model is led by preventive cardiology in collaboration with endocrinology and primary care. Support staff includes advance practice providers, nurse navigators, certified diabetes educators, dietitians, and pharmacists. Individualized treatment plans aim for “aggressive secondary risk reduction,” Dr. Kosiborod noted.
Six-month data from the Cardiometabolic Center Alliance show an increase from 28.2% at baseline to 67.1% (P < .0001) in prescribing of a four-agent guideline-directed medical therapy “bundle,” including the three from COORDINATE-Diabetes plus an antiplatelet or anticoagulant agent. Dr. Kosiborod presented these data during the ADA meeting in a poster.
Remaining questions involve sustainability, scalability, and system transformation, which require buy-in from multiple stakeholders, he noted.
He contends that it can be done. A prior example of “rapid and lasting care transformation” occurred in November 2006 with the launch of the “Door to Balloon (D2B) Alliance for Quality,” which dramatically increased the proportion of patients who received primary angioplasty within 90 minutes at hospitals around the United States. From January 2005 to September 2010, those proportions rose from 27.3% to 70.4%.
“Patients were coming into the emergency department with myocardial infarctions and waiting for hours before the interventional cardiologist came. The community said we needed a nationwide quality improvement initiative. ... Almost every hospital in the country changed their systems of care. It was a huge national effort. ... When we no longer consider the status quo acceptable, we can actually make something very special happen very quickly.”
After the session, Dr. Kosiborod said in an interview that the Cardiometabolic Center Alliance is now gathering data to make the financial case for the approach.
“We’re trying to develop a model that tells the admins which patients will save money, because, of course, if you can create a financial incentive, it only makes it go faster. ... We want to synchronize it in the best way possible.”
Dr. Lingvay has receiving nonfinancial support and grants from Novo Nordisk, personal fees or nonfinancial support from Sanofi, Lilly, Boehringer Ingelheim, Merck/Pfizer, Mylan, AstraZeneca, Johnson & Johnson, Intercept, Target Pharma, Zealand, Shionogi, Carmot, Structure, Bayer, Mediflix, WebMD, GI Dynamics, Intarcia Therapeutics, Mannkind, Novartis, Structure Therapeutics, and Valeritas. Dr. Kosiborod is a consultant for Alnylam Pharmaceuticals, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, ESPERION Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Novo Nordisk, Pharmacosmos, Pfizer, Sanofi, Vifor Pharma Management, and Youngene Therapeutics. He also receives research support from AstraZeneca and Boehringer Ingelheim. Dr. Eckel serves on consulting/advisory boards for Amgen, Arrowhead, Better, Ionis, Kowa, Lexicon, Novo Nordisk, Precision BioSciences, The Healthy Aging Company, Tolmar, and Weight Watchers.
A version of this article first appeared on Medscape.com.
SAN DIEGO – at the annual scientific sessions of the American Diabetes Association.
A symposium there focused on the recent randomized, controlled COORDINATE-Diabetes trial, which investigated a multipronged educational intervention in 43 U.S. cardiology clinics aimed at improving prescribing of guideline-recommended treatments for people with both type 2 diabetes and cardiovascular disease. Compared with clinics that were randomly assigned to offer usual care, the intervention significantly increased recommended prescribing of high-intensity statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ARBs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors and/or glucagonlike peptide 1 receptor agonists (GLP-1 agonists).
COORDINATE-Diabetes was aimed at cardiologists, who typically see these patients more often than do endocrinologists. However, the results are relevant to all health care providers involved in the care of those with type 2 diabetes, speakers argued at the ADA symposium.
“This is a cardiology study. I think it’s safe to say that not too many of you in the room are cardiologists. So why would you care about the results of the COORDINATE study?” said Ildiko Lingvay, MD, of the University of Texas Southwestern Medical Center, Dallas.
Dr. Lingvay went on to outline reasons that the COORDINATE findings apply to endocrinologists and primary care clinicians, as well as cardiologists. For one, a study from her institution that was presented at a recent internal medicine meeting showed that, among more than 10,000 patients with type 2 diabetes and cardiovascular disease, heart failure, and/or chronic kidney disease, the proportion of patients who were prescribed the appropriate guideline-indicated medications was 20.1% for those seen in primary care, 24.8% in endocrinology, 20.3% in cardiology, and 18.3% in nephrology.
“So, we [endocrinologists are] not that much better [than other specialties]” at prescribing, she noted.
Mikhail N. Kosiborod, MD, in independent commentary called the COORDINATE trial and other similar initiatives “the beginning of care transformation.”
The COORDINATE-Diabetes results were originally presented in March at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published in JAMA.
‘They’ve shown we can do better’
Asked to comment, Robert H. Eckel, MD, said in an interview, “I look at COORDINATE as a wake-up call to the need for multispecialty approaches to people with type 2 diabetes and cardiovascular disease. ... I think it’s a step in the door.”
Dr. Eckel, who has long advocated for a new “cardiometabolic” physician subspecialty, noted that COORDINATE-Diabetes “stopped short of training health care providers in the science and medicine of cardio-renal-metabolic disease.”
Nonetheless, regarding the efforts toward a more coordinated system of care, Dr. Eckel said, “I support the concept, unequivocally.” He is associated with the division of endocrinology, metabolism, and diabetes, University of Colorado at Denver, Aurora.
But the cost-effectiveness of the intervention “requires time to assess,” he added. “We don’t know anything yet other than [that] managing drug administration to meet goals that relate to outcomes in people with diabetes can be accomplished. They’ve shown that we can do better.”
Why should you care about a cardiology study?
In COORDINATE-Diabetes, 20 of the centers were randomly assigned to provide five interventions: assess local barriers, develop care pathways, coordinate care, educate clinicians, report data back to the clinics, and provide tools for the 459 participants. The other 23 clinics, with 590 participants, were randomly assigned to provide usual care per practice guidelines.
The primary outcome was the proportion of participants that prescribed all three groups of the recommended therapies at 6-12 months after enrollment; 37.9% prescribed the intervention, and 14.5% provided usual care, a significant 23% difference (P < .001). The rate of prescriptions of each of the three individual drug groups was also significantly higher with the intervention. No differences were seen in cardiovascular risk factors or outcomes.
Dr. Lingvay pointed out that the interventions tested in COORDINATE – such as fact sheets and medication passports for patients, system audits and feedback, and provider grand rounds – can be extrapolated to any specialist setting.
She added that the long-held model of team-based care means that “everyone involved in the care of these patients is responsible for ensuring best practices are followed.” Part of that, she said, is helping other specialists prescribe the same medications and communicate across the team.
For all specialists, she recommends using the resources available on the COORDINATE website.
‘It’s not a silver bullet; additional solutions are needed’
In his commentary, Dr. Kosiborod, executive director of the Cardiometabolic Center Alliance, noted, “The treatments studied in COORDINATE represent the biggest advances in a generation when it comes to improving outcomes in this population. ... We’re living in a renaissance age with the number of tools we have available. ... It’s getting better every day.”
Moreover, all the relevant professional society guidelines now recommend GLP-1 agonists and SGLT2 inhibitors. “And yet, when we look, less than 1 in 10 patients with type 2 diabetes and atherosclerotic cardiovascular disease are getting appropriate recommended care. One of the lessons of COORDINATE is that this needs to change if we’re really going to improve our patients’ lives.”
The barriers aren’t simply financial, Dr. Kosiborod said. He pointed to two studies that show that even reducing out-of-pocket costs resulted in only modest increases in adherence.
Educational gaps on the part of both clinicians and patients also factor in, as do misaligned incentives.
“Clinicians get paid for how many things they do, not necessarily how well they do them. Everyone wants to do the right thing, but ultimately, incentives do matter,” he emphasized.
While the COORDINATE-Diabetes interventions addressed several of the barriers, two-thirds of the participants still did not receive optimal therapy.
“It’s not a silver bullet. ... Additional solutions are needed,” Dr. Kosiborod observed.
Transformation occurs ‘when the status quo is no longer acceptable’
Enter his institution, the Cardiometabolic Center Alliance, part of Saint Luke’s Mid-America Heart Institute. The nonprofit system, which currently has 16 subscribing clinics around the country, offers patient-centered “team-based, coordinated, comprehensive care” for people with both type 2 diabetes and cardiovascular disease.
The model is led by preventive cardiology in collaboration with endocrinology and primary care. Support staff includes advance practice providers, nurse navigators, certified diabetes educators, dietitians, and pharmacists. Individualized treatment plans aim for “aggressive secondary risk reduction,” Dr. Kosiborod noted.
Six-month data from the Cardiometabolic Center Alliance show an increase from 28.2% at baseline to 67.1% (P < .0001) in prescribing of a four-agent guideline-directed medical therapy “bundle,” including the three from COORDINATE-Diabetes plus an antiplatelet or anticoagulant agent. Dr. Kosiborod presented these data during the ADA meeting in a poster.
Remaining questions involve sustainability, scalability, and system transformation, which require buy-in from multiple stakeholders, he noted.
He contends that it can be done. A prior example of “rapid and lasting care transformation” occurred in November 2006 with the launch of the “Door to Balloon (D2B) Alliance for Quality,” which dramatically increased the proportion of patients who received primary angioplasty within 90 minutes at hospitals around the United States. From January 2005 to September 2010, those proportions rose from 27.3% to 70.4%.
“Patients were coming into the emergency department with myocardial infarctions and waiting for hours before the interventional cardiologist came. The community said we needed a nationwide quality improvement initiative. ... Almost every hospital in the country changed their systems of care. It was a huge national effort. ... When we no longer consider the status quo acceptable, we can actually make something very special happen very quickly.”
After the session, Dr. Kosiborod said in an interview that the Cardiometabolic Center Alliance is now gathering data to make the financial case for the approach.
“We’re trying to develop a model that tells the admins which patients will save money, because, of course, if you can create a financial incentive, it only makes it go faster. ... We want to synchronize it in the best way possible.”
Dr. Lingvay has receiving nonfinancial support and grants from Novo Nordisk, personal fees or nonfinancial support from Sanofi, Lilly, Boehringer Ingelheim, Merck/Pfizer, Mylan, AstraZeneca, Johnson & Johnson, Intercept, Target Pharma, Zealand, Shionogi, Carmot, Structure, Bayer, Mediflix, WebMD, GI Dynamics, Intarcia Therapeutics, Mannkind, Novartis, Structure Therapeutics, and Valeritas. Dr. Kosiborod is a consultant for Alnylam Pharmaceuticals, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, ESPERION Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Novo Nordisk, Pharmacosmos, Pfizer, Sanofi, Vifor Pharma Management, and Youngene Therapeutics. He also receives research support from AstraZeneca and Boehringer Ingelheim. Dr. Eckel serves on consulting/advisory boards for Amgen, Arrowhead, Better, Ionis, Kowa, Lexicon, Novo Nordisk, Precision BioSciences, The Healthy Aging Company, Tolmar, and Weight Watchers.
A version of this article first appeared on Medscape.com.
AT ADA 2023
‘Artificial pancreas’ for all type 1 diabetes pregnancies?
In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.
Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.
The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.
CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”
The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.
Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”
However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
Two experts weigh in
Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.
“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.
“If a woman is on an AID system – except for DIY loop – I have them stop the automation and adjust manually,” she said in an email. “My [patients] do amazingly well in pregnancy – most can get their A1cs below 6%,” she noted. “But if someone can’t do that and their A1cs are higher, automation can help.
“It is always about individualizing care,” said Dr. Peters. “The one thing that helps the most is continuous glucose monitoring (CGM). And I do have patients who remain on [insulin] injections throughout pregnancy.”
And Sarit Polsky, MD, MPH, who was also not involved with the current study, agrees that “AID with CamAPS, which has an option to customize the glucose target in the pregnancy-specific range, appears to be safe and effective in pregnancy and should be offered” to patients in Europe and the United Kingdom.
“Whether other AID systems should be recommended in pregnancy is still unclear, said Dr. Polsky, associate professor of medicine and pediatrics at Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus.
“Around 48% of [global] pregnancies are unplanned,” Dr. Polsky said in an interview. “Many women do indeed become pregnant while using AID systems and many opt to continue use of these systems.
“Off-label use of these products can be beneficial in pregnancy in select cases, but the systems generally need the use of assistive techniques, which we previously published, to help get glucose levels to pregnancy-specific targets,” she noted in an email.
Study rationale, method, and findings
Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.
“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.
Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin.
As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.
Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.
They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.
A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).
Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.
The effect was consistent across clinical sites and maternal age and A1c categories.
Ongoing studies, off-label use
Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”
There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.
The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.
“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.
“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.
The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.
A version of this article first appeared on Medscape.com.
In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.
Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.
The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.
CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”
The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.
Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”
However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
Two experts weigh in
Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.
“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.
“If a woman is on an AID system – except for DIY loop – I have them stop the automation and adjust manually,” she said in an email. “My [patients] do amazingly well in pregnancy – most can get their A1cs below 6%,” she noted. “But if someone can’t do that and their A1cs are higher, automation can help.
“It is always about individualizing care,” said Dr. Peters. “The one thing that helps the most is continuous glucose monitoring (CGM). And I do have patients who remain on [insulin] injections throughout pregnancy.”
And Sarit Polsky, MD, MPH, who was also not involved with the current study, agrees that “AID with CamAPS, which has an option to customize the glucose target in the pregnancy-specific range, appears to be safe and effective in pregnancy and should be offered” to patients in Europe and the United Kingdom.
“Whether other AID systems should be recommended in pregnancy is still unclear, said Dr. Polsky, associate professor of medicine and pediatrics at Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus.
“Around 48% of [global] pregnancies are unplanned,” Dr. Polsky said in an interview. “Many women do indeed become pregnant while using AID systems and many opt to continue use of these systems.
“Off-label use of these products can be beneficial in pregnancy in select cases, but the systems generally need the use of assistive techniques, which we previously published, to help get glucose levels to pregnancy-specific targets,” she noted in an email.
Study rationale, method, and findings
Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.
“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.
Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin.
As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.
Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.
They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.
A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).
Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.
The effect was consistent across clinical sites and maternal age and A1c categories.
Ongoing studies, off-label use
Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”
There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.
The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.
“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.
“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.
The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.
A version of this article first appeared on Medscape.com.
In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.
Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.
The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.
CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”
The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.
Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”
However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
Two experts weigh in
Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.
“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.
“If a woman is on an AID system – except for DIY loop – I have them stop the automation and adjust manually,” she said in an email. “My [patients] do amazingly well in pregnancy – most can get their A1cs below 6%,” she noted. “But if someone can’t do that and their A1cs are higher, automation can help.
“It is always about individualizing care,” said Dr. Peters. “The one thing that helps the most is continuous glucose monitoring (CGM). And I do have patients who remain on [insulin] injections throughout pregnancy.”
And Sarit Polsky, MD, MPH, who was also not involved with the current study, agrees that “AID with CamAPS, which has an option to customize the glucose target in the pregnancy-specific range, appears to be safe and effective in pregnancy and should be offered” to patients in Europe and the United Kingdom.
“Whether other AID systems should be recommended in pregnancy is still unclear, said Dr. Polsky, associate professor of medicine and pediatrics at Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus.
“Around 48% of [global] pregnancies are unplanned,” Dr. Polsky said in an interview. “Many women do indeed become pregnant while using AID systems and many opt to continue use of these systems.
“Off-label use of these products can be beneficial in pregnancy in select cases, but the systems generally need the use of assistive techniques, which we previously published, to help get glucose levels to pregnancy-specific targets,” she noted in an email.
Study rationale, method, and findings
Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.
“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.
Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin.
As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.
Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.
They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.
A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).
Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.
The effect was consistent across clinical sites and maternal age and A1c categories.
Ongoing studies, off-label use
Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”
There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.
The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.
“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.
“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.
The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.
A version of this article first appeared on Medscape.com.
FROM ADA 2023