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Albiglutide, a GLP-1 Receptor Agonist, Effective in Various Treatment Scenarios in Patients with Type 2 Diabetes

August 2013, Vol 6 ADA 2013 Highlights - Emerging Therapies

Chicago, IL—A series of 8 phase 3 clinical trials that compared albiglutide, an investigational glucagon-like peptide (GLP)-1 receptor agonist, with 5 currently used treatment scenarios showed the drug effectively lowered hemoglobin (Hb) A1c, the primary outcome of the studies, in patients with uncontrolled type 2 diabetes. Albiglutide is administered once weekly, via an easy-to-use injection pen.

Philip D. Home, DPhil, DM, Professor of Diabetes Medicine, Newcastle University, England, and lead investigator of the HARMONY 5 study, said, “Albiglutide can be used throughout the stepped algorithm of therapy, from immunotherapy to combination,” based on the results of the HARMONY 1 to 5 studies, which were presented as late-breaking abstracts at the 2013 American Diabetes Association annual meeting. “Albiglutide compared to placebo is as effective as other glucose-lowering agents, and does not cause weight gain,” he said.

Dr Home noted that in the series of studies, the incidence of nausea and vomiting were relatively low, and that this was an improvement against other GLP-1 drugs. Although there were some injection-site reactions in the 5 trials, he thinks that this is re­lated more to the volume of the once-weekly injection, and that these “are not allergic reactions, [and] this particular preparation is very non-immunogenic.”

“There were no specific consistent side effects which caused withdrawal,” Dr Home noted, from the drug in these studies. Weight loss was less with albiglutide compared with the other GLP-1 drugs (ie, eventide, liraglutide [Victoza]).

In the HARMONY 1 study, when added to pioglitazone, with or without metformin, albiglutide 30 mg once weekly significantly reduced HbA1c in patients with diabetes from baseline to week 52 compared with placebo. The mean difference in the HbA1c reduction was –0.75% between the 2 groups (mean age, 55 years), a baseline HbA1c of 8.1%, a body mass index of 34 kg/m2, and an 8-year diabetes duration.

In the HARMONY 2 study, albiglutide monotherapy significantly reduced HbA1c levels in patients whose diabetes was uncontrolled with diet and exercise and who had not received antihyperglycemic drug treatment. At week 52, the mean difference in HbA1c reduction was –0.84% with albiglutide 30 mg versus placebo, and –1.04 with albiglutide 50 mg. The patient profile was similar to HARMONY 1, but the diabetes duration was 4 years. The significant reductions in fasting plasma glucose (FPG) at week 52 mirrored the reductions in HbA1c (–34 mg/dL for albiglutide 30 mg and –43 mg/dL for albiglutide 50 mg). The patients’ weight was reduced in each group (–0.7 kg with placebo, –0.4 kg with albiglutide 30 mg, and –0.9 kg with albiglutide 50 mg). The rates of injection-site reaction were 10% with placebo, 18% with albiglutide 30 mg, and 22% with albiglutide 50 mg.

In patients with uncontrolled type 2 diabetes who were receiving metformin, HARMONY 3 compared the effect of adding albiglutide 30 mg, sitagliptin, sulfonylurea, or placebo on the reduction of HbA1c at 104 weeks. The mean differences in HbA1c and FPG levels with albiglutide versus the comparators are shown in the Table. Weight loss was significantly greater with albiglutide compared with sulfonylurea, and the rates of adverse events were similar across the groups.


Table

The HARMONY 4 trial showed that albiglutide was noninferior to insulin glargine for the primary outcome of change in HbA1c at week 52 in patients with uncontrolled diabetes who were using metformin with and without sulfonylurea. Albiglutide and glargine were uptitrated as needed according to a predefined schema. Injection-site reaction was 13.9% with once-weekly albiglutide and 8.7% with once-daily glargine. The patients were similar to those in HARMONY 1, but 82% of patients were taking metformin plus a sulfonylurea. Albiglutide significantly reduced weight and the rates of hypoglycemia; nausea was higher, and 1 patient had pancreatitis. The change in FPG was greater with glargine than with albiglutide.

Triple therapy with albiglutide was tested in HARMONY 5. In patients taking metformin and glimepiride, the reduction in HbA1c at week 52 was –0.55% with albiglutide, –0.80% with pioglitazone, and –0.33% with placebo. The FPG changes were –12.4 mg/dL, –31.4 mg/dL, and +11.5 mg/dL, respectively. Patients taking albiglutide or placebo lost 0.4 kg, whereas those taking pioglitazone gained 4.4 kg.

Dr Home said that the use of GLP-1 drugs will increase, particularly in combination with insulin therapy, because there is more evidence of their benefit. The success with liraglutide has offset the lesser success with exenatide, because of its high rate of nausea and vomiting. Yet, he noted that the issue of whether GLP-1 agents cause pancreatitis and pancreatic cancer remains to be resolved. “I think GLP-1 drugs are particularly useful for people who have glucose control problems, obesity-related problems, or problems managing their body weight,” he said.

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