Investigational Agent Dulaglutide versus Exenatide and Placebo

Chicago—After 26 weeks of treatment, patients with type 2 diabetes who received dulaglutide once weekly had a statistically significant reduction in hemoglobin A1c (HbA1c) levels compared with a placebo group and patients who took exenatide, according to a randomized, placebo-controlled, phase 3 trial.

Carol Wysham, MD, the study’s lead author, presented the results at the ADA meeting in an oral abstract session. Eli Lilly, manufacturer of dulaglutide, funded the study.

Dulaglutide, an investigational long-acting glucagon-like peptide-1 (GLP-1) receptor analog, is being tested for once-weekly use in patients with type 2 diabetes. Eli Lilly expects to submit dulaglutide data to the FDA for approval later this year. Exenatide is an FDA-approved GLP-1 receptor agonist used in combination with diet and exercise to improve glycemic control in patients with type 2 diabetes.

In this study, the authors randomized 976 patients in a 2:2:2:1 ratio to receive 1.5 mg of dulaglutide, 0.75 mg of dulaglutide, exenatide, or placebo. After 26 weeks, patients in the placebo group were randomized to receive either of the dulaglutide doses. The main analysis was completed after 26 weeks, but the extension phase lasted until week 52. Patients also received maximum tolerated doses of 1500-mg to 3000-mg metformin and 30-mg to 45-mg pioglitazone.

Patients were included if they had an HbA1c level of at least 7.0%, a body mass index (BMI) from 23 kg/m² to 45 kg/m², and no increase or decrease in body weight of ≥5% for at least 3 months. Mean age was approximately 55 years, mean BMI was approximately 33 kg/m², and mean duration of type 2 diabetes was 8.8 years. Approximately 75% were white and 40% were female.

At week 26, patients in the 1.5-mg dulaglutide group had a mean reduction in HbA1c from baseline of 1.51% compared with a mean reduction of 0.46% in the placebo group (P<.001) and a mean reduction of 0.99% in the exenatide group (P<.001). In addition, the mean HbA1c reduction from baseline to week 26 was 1.3% in the 0.75-mg dulaglutide group, which was significantly better than in the placebo group (P<.001) and in the exenatide group (P<.001). The efficacy of the dulaglutide doses in reducing HbA1c levels was maintained up to week 52, according to Dr. Wysham.

In addition, 45% of patients in the placebo group had an HbA1c level <7.0% after 26 weeks, which was significantly lower than the 79% of patients in the 1.5-mg dulaglutide group (P<.001) and the 67% of patients in the 0.75-mg dulaglutide group (P<.001). There were also significant reductions in fasting serum glucose in both of the dulaglutide groups compared with the placebo group as well as the exenatide group (P<.001 in both comparisons).

At 26 weeks, the percentage of patients in each group with adverse events was similar: 77.1% in the 1.5-mg dulaglutide group, 71.1% in the 0.75-mg dulaglutide group, 71.7% in the exenatide group, and 73.8% in the placebo group. Dr. Wysham noted that the majority of adverse events were gastrointestinal, including nausea, vomiting, and diarrhea. She also mentioned there were low rates of injection site reactions (ranging from 1.4% to 4.7%) and hypoglycemia (ranging from 2.3% to 5.9%).