Efficacy and Safety of an Expanded Dulaglutide Dose Range—A Phase 2, Placebo-Controlled Trial in T2D Patients on Metformin

Dulaglutide is approved at two doses (0.75 and 1.5 mg) for treatment of T2D. There has been limited assessment of higher doses. We hypothesized that higher doses of dulaglutide may provide further improvement in glucose and body weight control. In this study, 3 and 4.5 mg doses were evaluated for safety/efficacy after 18 weeks (weeks) of treatment, including a 6 week dose escalation. Patients (N=318) on ≥1500 mg metformin, were randomized (1:1:1:1) to placebo (n=82), dulaglutide 1.5 mg (n=81), dulaglutide 3 mg (n=79), dulaglutide 4.5 mg (n=76). The primary objective was superiority of dulaglutide doses over placebo in HbA1c reduction at 18 weeks. Table 1 presents the primary and selected secondary efficacy data. Reductions in HbA1c and body weight were significant for each dose vs. placebo. Incidence of gastrointestinal events (mostly mild to moderate) were dose-dependent for nausea (placebo, 4.9%; dulaglutide 1.5 mg, 22.2%; dulaglutide 3 mg, 24.1%; dulaglutide 4.5 mg, 30.3%) but not for vomiting (placebo 4.9%; dulaglutide 1.5 mg, 11.1%; dulaglutide 3 mg, 10.1%; dulaglutide 4.5 mg, 13.2%). No patients experienced severe hypoglycemia. The results of this trial show that 3 mg and 4.5 mg doses, compared to the 1.5 mg dose, may provide additional glycemic benefit and weight reduction with an acceptable safety profile in treatment of T2D patients, providing support for further phase 3 development.