Compared with a combination of insulin glargine, metformin and glimepiride, once-weekly dulaglutide demonstrated superiority and noninferiority as a type 2 diabetes therapy with two different doses, according to research presented at the 50th European Association for the Study of Diabetes Annual Meeting.
In the randomized phase 3, 78-week, parallel-arm, open-label AWARD-2 trial, dulaglutide 1.5 mg was superior, and 0.75 mg noninferior, to the combined treatment for glycemic control, and both were associated with weight loss, reduced incidence of hypoglycemia and acceptable safety profiles.
“Dulaglutide is an effective and safe alternative to insulin glargine in patients with type 2 diabetes treated with maximally tolerated doses of metformin and glimepiride and who show inadequate glycemic control,” said Francesco Giorgino, MD, PhD, of the University of Bari Aldo Moro in Italy.
Giorgino and colleagues equally assigned 807 patients (mean age, 57 years; diabetes duration, 9.1 years; HbA1c, 8.1%; body weight, 86.3 kg; BMI, 31.6 kg/m2) to dulaglutide 1.5 mg or dulaglutide 0.75 mg once per week, or insulin glargine once per day. A noninferiority margin of 0.4% for HbA1c change at 52 weeks was the primary endpoint, with additional analysis conducted at 52 and 78 weeks.
At 52 weeks, mean HbA1c decreased more with dulaglutide 1.5 mg (–1.08%) and dulaglutide 0.75 mg (–0.76%) compared with insulin glargine (–0.63%); patients reaching HbA1c <7% were: 53.3%, dulaglutide 1.5 mg; 37.1%, dulaglutide 0.75 mg; and 30.9%, insulin glargine. The mean insulin glargine dose was 29.4 U.
Body weight decreased with both dulaglutide doses (–1.87 kg, dulaglutide 1.5 mg; –1.33 kg, dulaglutide 0.75 mg) and increased with insulin glargine (1.44 kg). The mean rate of documented symptomatic hypoglycemia (≤3.9 mmol/L) during 52 weeks was 2 per patient/year for dulaglutide 1.5 mg and dulaglutide 0.75 mg, but 3.3 per patient/year for insulin glargine.
At 78 weeks, results remained similar for HbA1c, body weight and hypoglycemia, with a mean insulin glargine dose of 31.4 U. In this time, four severe hypoglycemic events occurred — two with dulaglutide 1.5 mg and two with insulin glargine.
Nausea and diarrhea were more common with dulaglutide 1.5 mg and dulaglutide 0.75 mg than insulin glargine.
“These gastrointestinal side effects are associated with treatment with glucagon-like peptide-1 receptor agonists,” Giorgino said. “There were very few injection-site reactions with the GLP-1 tested in this study, and the cases of adjudicated pancreatitis were three in two arms of dulaglutide treatment — one a case of chronic pancreatitis.”
For more information:
Giorgino F. Abstract #38. Presented at: 50th EASD Annual Meeting; Sept. 16-19, 2014; Vienna.
Disclosure: The study was supported by Eli Lilly and Company. Giorgino reports serving as a member of the advisory board and speakers’ bureau for, and receiving research support from, for Eli Lilly and various pharmaceutical companies, for some of which he also serves as a consultant.