• Diabetes Mellitus
• Diabetes & Endocrinology Clinical Trials

• Diabetes Mellitus
• Diabetes & Endocrinology Clinical Trials
• Endocrinology
• Diabetes & Metabolic Syndrome

Treatment with albiglutide in combination with metformin was superior to sitagliptin and glimepiride for reduction of HbA1Cand fasting plasma glucose (FPG) levels in patients with type 2 diabetes mellitus (T2DM). Murray Stewart, MD, GlaxoSmithKline, Upper Merion, Pennsylvania, USA, presented data from the Efficacy and Safety of Albiglutide in Treatment of Type 2 Diabetes trial [HARMONY 3; NCT00838903].

A long-acting glucagon-like peptide 1 receptor agonist, albiglutide is being evaluated in patients with T2DM in a series of 8 trials. The purpose of the HARMONY 3 trial was to determine the efficacy and safety of albiglutide compared with placebo, sitagliptin, or glimepiride in patients with T2DM currently taking metformin.

In the double-blind Phase 3 HARMONY 3 trial, 1012 patients were randomized to receive 30 mg of once-weekly albiglutide, 100 mg of once-daily sitagliptin, 2 to 4 mg of once-daily glimepiride, or placebo once weekly for 104 weeks. All patients received up to 1 g of metformin. The mean age at study initiation was 54.5 years and at baseline patients had a mean body mass index (BMI) of 32.6 kg/m², mean weight of 90.7 kg, and a mean 6 years of diabetes duration [Johnson S et al. EASD 2013 (abstr 5)].

The primary endpoint of the HARMONY 3 study was HbA1C change from baseline at 104 weeks. The secondary endpoints included change in HbA1C from baseline over time, change in FPG over time, change in body weight from baseline over time, proportion of patients that reached the HbA1C goal, and time to hypoglycemia rescue.

Patients treated with albiglutide demonstrated a mean −6.89 change in HbA1C from baseline (95% CI, −8.31 to −5.57), treatment with sitagliptin resulted in a −3.06 change (95% CI, −4.48 to −1.64), and treatment with glimepiride resulted in a −3.94% change (95% CI, −5.36 to −2.62), compared with a 2.95% change from baseline in patients treated with placebo (95% CI, 0.55 to 5.47). Albiglutide treatment resulted in a significant decrease in FPG compared with sitagliptin (−0.86; 95% CI, −1.30 to −0.41; p=0.0002), glimepiride (−0.56; 95% CI, −1.01 to −0.12; p=0.0133), and placebo (−1.53; 95% CI, −2.16 to −0.90; p<0.0001).

Adverse events were similar among treatment groups and included nausea, diarrhea, and vomiting. Injection-site reactions occurred in 17.2% of patients in the albiglutide arm, 6% in the sitagliptin arm, 8% in the glimepiride arm, and 5% in the placebo arm. There were no severe hypoglycemic events; however, prerescue documented symptomatic hypoglycemia was reported in 3%, 2%, and 18% of patients treated with albiglutide, sitagliptin, and glimepiride, respectively, compared with 4% of patients who received placebo.

Pancreatitis occurred in four patients who received albiglutide and two patients who received glimepiride; pancreatitis was determined to be possibly associated to the study drug in two patients who received albiglutide. In addition, one patient treated with albiglutide and two patients treated with sitagliptin developed thyroid cancer during the study.

Dr. Stewart indicated that, in his opinion, the data from the HARMONY 3 trial suggest that albiglutide in combination with metformin was superior to add-on therapy with sitagliptin or glimepiride for a decrease in HbA1C and FPG.

• © 2013 MD Conference Express®