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

Abstract

AimTo 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 methodsIn this phase II, randomized, placebo‐controlled, double‐blind trial, participants with a body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 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.ResultsOver 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.ConclusionsEfpeglenatide 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.

Weight Loss and Maintenance Related to the Mechanism of Action of Glucagon-Like Peptide 1 Receptor Agonists

“…Patients receiving semaglutide 2.4 mg in this trial lost 9.9% of their body weight, compared with 0.4% in those receiving placebo [33]. In a phase II study of the longacting GLP-1RA efpeglenatide (4 mg once weekly, 6 mg once weekly, 6 mg once every 2 weeks, and 8 mg once every 2 weeks), patients with obesity and without diabetes had statistically significant reductions in body weight compared with placebo after 20 weeks of treatment (differences in least squares means were -6.3 to -7.2 kg; p \ 0.0001) [36].…”

Incretin Hormones in Obesity and Related Cardiometabolic Disorders: The Clinical Perspective

“…The highest placebo-adjusted weight loss was −7.2 kg for a group receiving 6 mg of efpeglenatide once weekly. Gastrointestinal effects were the most common side effects [ 202 ]. Another medication that can be a potential anti-obesity drug is MEDI0382—a GLP-1 and glucagon receptor dual agonist.…”

Effects of efpeglenatide versus liraglutide on gastric emptying, glucose metabolism and beta-cell function in people with type 2 diabetes: an exploratory, randomized phase Ib study

“…13 14 Efpeglenatide also has unique receptor properties that may explain the greater maximal GLP-1 receptor signaling and reduced desensitization seen with efpeglenatide versus other GLP-1 RAs following chronic exposure in biochemical and preclinical studies. 15 16 Three phase II studies that examined efpeglenatide in both people with T2D 13 14 and people with obesity without T2D 17 found that efpeglenatide was associated with significant decreases in glycated hemoglobin (HbA 1c ) and body weight. With weekly dosing, efpeglenatide was generally well tolerated; the most common AEs were GI disorders, which is consistent with the safety profile of the GLP-1 RA class.…”