Efficacy and safety of once‐monthly efpeglenatide in patients with type 2 diabetes: Results of a phase 2 placebo‐controlled, 16‐week randomized dose‐finding study

AIMS: To determine the optimal dose(s) of once‐monthly administration of efpeglenatide, a long‐acting glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), in patients with type 2 diabetes (T2D) inadequately controlled on metformin. MATERIALS AND METHODS: In this phase 2, randomized, placebo‐controlled, double‐blind trial (NCT02081118), patients were randomized 1:1:1:1 to subcutaneous efpeglenatide (8, 12 or 16 mg once monthly; n = 158) or placebo (n = 51). The 16‐week treatment period included a 4‐week titration phase with once‐weekly efpeglenatide 4 mg, followed by one dose of efpeglenatide 8 mg once monthly and two doses of the assigned once‐monthly dose. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to week 17. RESULTS: All efpeglenatide doses significantly reduced HbA1c versus placebo (P < 0.0001 for all). Overall, the least squares mean difference in HbA1c reductions between efpeglenatide and placebo was −7.7 mmol/mol (−0.71%; baseline to week 17). At week 17, a significantly greater proportion of efpeglenatide patients had an HbA1c level <53 mmol/mol (<7%) versus placebo (48.7% vs. 30.6%; P = 0.0320). Significant body weight loss occurred across all efpeglenatide doses (placebo‐corrected reduction −2.0 kg [efpeglenatide overall]; P = 0.0003). The safety profile was consistent with GLP‐1RAs, with gastrointestinal (GI) disorders being the most common treatment‐emergent adverse events. Fluctuations in effects on glucose levels and rates of GI events occurred between peak and trough efpeglenatide concentrations. CONCLUSIONS: Efpeglenatide once monthly (following once‐weekly titration) has significant benefits with regard to HbA1c and weight reduction versus placebo in patients with T2D. Further studies are needed to evaluate the long‐term efficacy and safety of efpeglenatide once monthly.