Body weight management and safety with efpeglenatide in adults without diabetes: A phase II randomized study

Aim To evaluate the safety of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), and its effects on body weight management in adults without diabetes. Materials and methods In this phase II, randomized, placebo-controlled, double-blind trial, participants with a body mass index (BMI) >= 30 kg/m(2) or >= 27 kg/m(2) with comorbidity were randomized 1:1:1:1:1 to efpeglenatide (4 mg once weekly, 6 mg once weekly, 6 mg once every 2 wk, or 8 mg once every 2 wk; n = 237) or placebo (n = 60) in combination with a hypocaloric diet. The primary endpoint was body weight change from baseline after 20 wk of treatment, assessed using a mixed-effect model with repeated measures with an unstructured covariance matrix over all post-screening visits; treatment comparisons were based on least squares mean estimates. Results Over 20 wk, all doses of efpeglenatide significantly reduced body weight from baseline versus placebo (P < 0.0001), with placebo-adjusted reductions ranging between -6.3 kg (6 mg once every 2 wk) and -7.2 kg (6 mg once weekly). Greater proportions of efpeglenatide-treated participants had body weight loss of >= 5% or >= 10% versus placebo (P < 0.01, all comparisons). Efpeglenatide led to significant improvements in glycaemic variables (fasting plasma glucose and glycated haemoglobin) and lipid profiles (cholesterol, triglycerides) versus placebo. Rates of study discontinuations as a result of adverse events ranged from 5% to 19% with efpeglenatide. Gastrointestinal effects were the most common treatment-emergent adverse events. Conclusions Efpeglenatide once weekly and once every 2 wk led to significant body weight reduction and improved glycaemic and lipid variables versus placebo. It was also well tolerated for weight management in adults without diabetes.