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.
Mitchel L. Zoler
Dr. Murray W. Stewart
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.
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