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BARCELONA – Treatment of patients with type 2 diabetes with albiglutide plus metformin produced a significantly greater rate of glycemic control compared with three other oral regimens in a pivotal trial with more than 1,000 patients treated and followed for up to 2 years.
After 2 years of treatment, 59% of patients randomized to albiglutide, an investigational glucagonlike peptide–1 (GLP-1) receptor agonist, and metformin had a hemoglobin A1c level below 7.5%, compared with 49% of patients randomized to glimepiride plus metformin, 44% of patients randomized to sitagliptin plus metformin, and 28% who received metformin plus placebo. The differences between albiglutide and each of the three other study groups were statistically significant, Dr. Murray W. Stewart reported at the annual meeting of the European Association for the Study of Diabetes.
In addition, albiglutide treatment produced no severe hypoglycemic episodes and resulted in a relatively modest 5% incidence of nausea and vomiting during the first 8 weeks on treatment, "generally consistent with the known profile" of GLP-1 receptor agonists, Dr. Stewart said. During the second year of treatment, the incidence of nausea or vomiting in albiglutide-treated patients declined to a steady rate of about 1%-2%, similar to that of patients on sitagliptin or metformin plus placebo, and less than the 3%-4% rate seen among patients on glimepiride during the final 6 months of the study, he said. Dr. Stewart is senior vice president for metabolic pathways and cardiovascular therapy at GlaxoSmithKline, the company developing albiglutide.
The HARMONY 3 trial randomized 1,049 patients with type 2 diabetes and hyperglycemia, with an average HbA1c level of 8.1%. The study started all patients on metformin and up-titrated their regimen to a maximum tolerated dosage over 2 weeks, and also started all patients on a diet and exercise regimen for a week prior to randomization. After these two run-in treatments began, the investigators randomized patients to receive either 30 mg of albiglutide by injection once a week, sitagliptin (Januvia, a dipeptidyl peptidase–4 inhibitor) at 100 mg orally once per day, glimepiride (Amaryl, a sulfonylurea) at 2-4 mg orally once a day, or a weekly placebo injection. About two thirds of patients completed the study’s full 2 years of treatment. Study patients averaged about 55 years old, their mean body mass index was 33 kg/m2, and they had type 2 diabetes for an average of about 6 years.
After 2 years, the average HbA1c level was about 7.5% in the patients on albiglutide, 7.8% in the patients on sitagliptin or glimepiride, and 8.4% among those on metformin plus placebo. All patients lost an average of about 1 kg of weight at 2 years compared with baseline except those who receive glimepiride, whose weight increased by an average of about 1 kg. The incidence of patients having their HbA1c rise to 8.5%, requiring the initiation of insulin therapy, was 26% in patients on albiglutide, 33% of those on glimepiride, 36% among those on sitagliptin, and 59% of those on metformin plus placebo, all significant differences between albiglutide and each of the three comparator arms.
Symptomatic hypoglycemia occurred in 3% of the albiglutide patients, similar to the rates in the sitagliptin and placebo subgroups, and less than the 18% rate among patients who received glimepiride. Injection-site reactions occurred in 17% of the albiglutide patients, but these were mostly mild or moderate, and 21 patients on this drug developed antialbiglutide antibodies. Two patients on albiglutide had probable pancreatitis that was at least possibly related to their treatment, and one patient developed thyroid cancer.
The HARMONY 3 trial is one of several pivotal trials recently completed for albiglutide. GlaxoSmithKline initially filed an application with the Food and Drug Administration for approval of albiglutide last January. The goal date for an FDA decision is currently next April.
HARMONY 3 was sponsored by GlaxoSmithKline. Dr. Stewart is an employee of the company.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
In this study, albiglutide showed less weight loss than we have seen in the results from studies of other GLP-1 receptor agonists; on the other hand, it was relatively free of adverse events other than some episodes of nausea and vomiting, which may be an attractive feature for some patients.
It is still too soon to know how this entire class of drugs will fit into the algorithm for treating patients with type 2 diabetes. The GLP-1 receptor agonists seem to produce glycemic control that is at least as good as that produced by insulin, but without causing severe hypoglycemia or much hypoglycemia of any kind, and also leading to a small amount of weight loss. The potential exists for the GLP-1 receptor agonists to supplant metformin as a first-line drug, but with a few qualifications.
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First, the most convincing evidence to support early use of the GLP-1 receptor agonists would be if they are shown in the future to be significantly better at preventing complications than metformin, especially cardiovascular and microvascular events.
There is also the issue of administration by injection. Some patients don’t like injections, and others may hesitate until they try it and find it is not very difficult. But patients who accept this route of delivery may find the GLP-1 receptor agonists to be effective and relatively safe. Of course, there is also the issue of the drug’s costs. Generic metformin will hold a price edge over all these new drugs for many years to come.
Dr. Michael A. Nauck is head of the Diabetes Center in Bad Lauterberg, Germany. He made these comments in an interview. He has been a coinvestigator on other trials of albiglutide and a consultant to GlaxoSmithKline, the company developing this drug, as well as a consultant to several other companies that are developing or that market drugs for patients with diabetes.
In this study, albiglutide showed less weight loss than we have seen in the results from studies of other GLP-1 receptor agonists; on the other hand, it was relatively free of adverse events other than some episodes of nausea and vomiting, which may be an attractive feature for some patients.
It is still too soon to know how this entire class of drugs will fit into the algorithm for treating patients with type 2 diabetes. The GLP-1 receptor agonists seem to produce glycemic control that is at least as good as that produced by insulin, but without causing severe hypoglycemia or much hypoglycemia of any kind, and also leading to a small amount of weight loss. The potential exists for the GLP-1 receptor agonists to supplant metformin as a first-line drug, but with a few qualifications.
|
|
First, the most convincing evidence to support early use of the GLP-1 receptor agonists would be if they are shown in the future to be significantly better at preventing complications than metformin, especially cardiovascular and microvascular events.
There is also the issue of administration by injection. Some patients don’t like injections, and others may hesitate until they try it and find it is not very difficult. But patients who accept this route of delivery may find the GLP-1 receptor agonists to be effective and relatively safe. Of course, there is also the issue of the drug’s costs. Generic metformin will hold a price edge over all these new drugs for many years to come.
Dr. Michael A. Nauck is head of the Diabetes Center in Bad Lauterberg, Germany. He made these comments in an interview. He has been a coinvestigator on other trials of albiglutide and a consultant to GlaxoSmithKline, the company developing this drug, as well as a consultant to several other companies that are developing or that market drugs for patients with diabetes.
In this study, albiglutide showed less weight loss than we have seen in the results from studies of other GLP-1 receptor agonists; on the other hand, it was relatively free of adverse events other than some episodes of nausea and vomiting, which may be an attractive feature for some patients.
It is still too soon to know how this entire class of drugs will fit into the algorithm for treating patients with type 2 diabetes. The GLP-1 receptor agonists seem to produce glycemic control that is at least as good as that produced by insulin, but without causing severe hypoglycemia or much hypoglycemia of any kind, and also leading to a small amount of weight loss. The potential exists for the GLP-1 receptor agonists to supplant metformin as a first-line drug, but with a few qualifications.
|
|
First, the most convincing evidence to support early use of the GLP-1 receptor agonists would be if they are shown in the future to be significantly better at preventing complications than metformin, especially cardiovascular and microvascular events.
There is also the issue of administration by injection. Some patients don’t like injections, and others may hesitate until they try it and find it is not very difficult. But patients who accept this route of delivery may find the GLP-1 receptor agonists to be effective and relatively safe. Of course, there is also the issue of the drug’s costs. Generic metformin will hold a price edge over all these new drugs for many years to come.
Dr. Michael A. Nauck is head of the Diabetes Center in Bad Lauterberg, Germany. He made these comments in an interview. He has been a coinvestigator on other trials of albiglutide and a consultant to GlaxoSmithKline, the company developing this drug, as well as a consultant to several other companies that are developing or that market drugs for patients with diabetes.
BARCELONA – Treatment of patients with type 2 diabetes with albiglutide plus metformin produced a significantly greater rate of glycemic control compared with three other oral regimens in a pivotal trial with more than 1,000 patients treated and followed for up to 2 years.
After 2 years of treatment, 59% of patients randomized to albiglutide, an investigational glucagonlike peptide–1 (GLP-1) receptor agonist, and metformin had a hemoglobin A1c level below 7.5%, compared with 49% of patients randomized to glimepiride plus metformin, 44% of patients randomized to sitagliptin plus metformin, and 28% who received metformin plus placebo. The differences between albiglutide and each of the three other study groups were statistically significant, Dr. Murray W. Stewart reported at the annual meeting of the European Association for the Study of Diabetes.
In addition, albiglutide treatment produced no severe hypoglycemic episodes and resulted in a relatively modest 5% incidence of nausea and vomiting during the first 8 weeks on treatment, "generally consistent with the known profile" of GLP-1 receptor agonists, Dr. Stewart said. During the second year of treatment, the incidence of nausea or vomiting in albiglutide-treated patients declined to a steady rate of about 1%-2%, similar to that of patients on sitagliptin or metformin plus placebo, and less than the 3%-4% rate seen among patients on glimepiride during the final 6 months of the study, he said. Dr. Stewart is senior vice president for metabolic pathways and cardiovascular therapy at GlaxoSmithKline, the company developing albiglutide.
The HARMONY 3 trial randomized 1,049 patients with type 2 diabetes and hyperglycemia, with an average HbA1c level of 8.1%. The study started all patients on metformin and up-titrated their regimen to a maximum tolerated dosage over 2 weeks, and also started all patients on a diet and exercise regimen for a week prior to randomization. After these two run-in treatments began, the investigators randomized patients to receive either 30 mg of albiglutide by injection once a week, sitagliptin (Januvia, a dipeptidyl peptidase–4 inhibitor) at 100 mg orally once per day, glimepiride (Amaryl, a sulfonylurea) at 2-4 mg orally once a day, or a weekly placebo injection. About two thirds of patients completed the study’s full 2 years of treatment. Study patients averaged about 55 years old, their mean body mass index was 33 kg/m2, and they had type 2 diabetes for an average of about 6 years.
After 2 years, the average HbA1c level was about 7.5% in the patients on albiglutide, 7.8% in the patients on sitagliptin or glimepiride, and 8.4% among those on metformin plus placebo. All patients lost an average of about 1 kg of weight at 2 years compared with baseline except those who receive glimepiride, whose weight increased by an average of about 1 kg. The incidence of patients having their HbA1c rise to 8.5%, requiring the initiation of insulin therapy, was 26% in patients on albiglutide, 33% of those on glimepiride, 36% among those on sitagliptin, and 59% of those on metformin plus placebo, all significant differences between albiglutide and each of the three comparator arms.
Symptomatic hypoglycemia occurred in 3% of the albiglutide patients, similar to the rates in the sitagliptin and placebo subgroups, and less than the 18% rate among patients who received glimepiride. Injection-site reactions occurred in 17% of the albiglutide patients, but these were mostly mild or moderate, and 21 patients on this drug developed antialbiglutide antibodies. Two patients on albiglutide had probable pancreatitis that was at least possibly related to their treatment, and one patient developed thyroid cancer.
The HARMONY 3 trial is one of several pivotal trials recently completed for albiglutide. GlaxoSmithKline initially filed an application with the Food and Drug Administration for approval of albiglutide last January. The goal date for an FDA decision is currently next April.
HARMONY 3 was sponsored by GlaxoSmithKline. Dr. Stewart is an employee of the company.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BARCELONA – Treatment of patients with type 2 diabetes with albiglutide plus metformin produced a significantly greater rate of glycemic control compared with three other oral regimens in a pivotal trial with more than 1,000 patients treated and followed for up to 2 years.
After 2 years of treatment, 59% of patients randomized to albiglutide, an investigational glucagonlike peptide–1 (GLP-1) receptor agonist, and metformin had a hemoglobin A1c level below 7.5%, compared with 49% of patients randomized to glimepiride plus metformin, 44% of patients randomized to sitagliptin plus metformin, and 28% who received metformin plus placebo. The differences between albiglutide and each of the three other study groups were statistically significant, Dr. Murray W. Stewart reported at the annual meeting of the European Association for the Study of Diabetes.
In addition, albiglutide treatment produced no severe hypoglycemic episodes and resulted in a relatively modest 5% incidence of nausea and vomiting during the first 8 weeks on treatment, "generally consistent with the known profile" of GLP-1 receptor agonists, Dr. Stewart said. During the second year of treatment, the incidence of nausea or vomiting in albiglutide-treated patients declined to a steady rate of about 1%-2%, similar to that of patients on sitagliptin or metformin plus placebo, and less than the 3%-4% rate seen among patients on glimepiride during the final 6 months of the study, he said. Dr. Stewart is senior vice president for metabolic pathways and cardiovascular therapy at GlaxoSmithKline, the company developing albiglutide.
The HARMONY 3 trial randomized 1,049 patients with type 2 diabetes and hyperglycemia, with an average HbA1c level of 8.1%. The study started all patients on metformin and up-titrated their regimen to a maximum tolerated dosage over 2 weeks, and also started all patients on a diet and exercise regimen for a week prior to randomization. After these two run-in treatments began, the investigators randomized patients to receive either 30 mg of albiglutide by injection once a week, sitagliptin (Januvia, a dipeptidyl peptidase–4 inhibitor) at 100 mg orally once per day, glimepiride (Amaryl, a sulfonylurea) at 2-4 mg orally once a day, or a weekly placebo injection. About two thirds of patients completed the study’s full 2 years of treatment. Study patients averaged about 55 years old, their mean body mass index was 33 kg/m2, and they had type 2 diabetes for an average of about 6 years.
After 2 years, the average HbA1c level was about 7.5% in the patients on albiglutide, 7.8% in the patients on sitagliptin or glimepiride, and 8.4% among those on metformin plus placebo. All patients lost an average of about 1 kg of weight at 2 years compared with baseline except those who receive glimepiride, whose weight increased by an average of about 1 kg. The incidence of patients having their HbA1c rise to 8.5%, requiring the initiation of insulin therapy, was 26% in patients on albiglutide, 33% of those on glimepiride, 36% among those on sitagliptin, and 59% of those on metformin plus placebo, all significant differences between albiglutide and each of the three comparator arms.
Symptomatic hypoglycemia occurred in 3% of the albiglutide patients, similar to the rates in the sitagliptin and placebo subgroups, and less than the 18% rate among patients who received glimepiride. Injection-site reactions occurred in 17% of the albiglutide patients, but these were mostly mild or moderate, and 21 patients on this drug developed antialbiglutide antibodies. Two patients on albiglutide had probable pancreatitis that was at least possibly related to their treatment, and one patient developed thyroid cancer.
The HARMONY 3 trial is one of several pivotal trials recently completed for albiglutide. GlaxoSmithKline initially filed an application with the Food and Drug Administration for approval of albiglutide last January. The goal date for an FDA decision is currently next April.
HARMONY 3 was sponsored by GlaxoSmithKline. Dr. Stewart is an employee of the company.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE EASD ANNUAL MEETING
Major finding: Treatment with metformin plus albiglutide dropped HbA1c below 7.5% in 59% of patients, compared with 28% for metformin plus placebo.
Data source: HARMONY 3, which randomized 1,049 patients with type 2 diabetes to treatment with metformin plus albiglutide, sitagliptin, glimepiride, or placebo and followed them for up to 2 years.
Disclosures: HARMONY 3 was sponsored by GlaxoSmithKline. Dr. Stewart is an employee of the company.
