A six month randomized, double-blind, placebo-controlled trial of weekly exenatide in adolescents with obesity

Background: Pharmacological treatment options for adolescents with obesity are very limited. Glucagon-like-peptide-1 (GLP-1) receptor-agonist could be a treatment option for adolescent obesity. Objective: To investigate the effect of exenatide extended-release on body-mass-index (BMI)- SDS as primary outcome, and glucose-metabolism, cardiometabolic risk factors liver steatosis, and other BMI metrics as secondary outcomes, and its safety and tolerability in adolescents with obesity. Methods: Six-months, randomized, double-blinded, parallel, placebo-controlled clinical trial in patients (n=44, 10-18 years, females n=22) with BMI-SDS>2.0 or age-adapted-BMI>30 kg/m² according to WHO were included. Patients received lifestyle intervention and were randomized to exenatide extended-release 2 mg (n=22) or placebo (n=22) sub-cutaneousinjections given once weekly. Oral-glucose-tolerance-tests (OGTT) were conducted at the beginning and end of the intervention. Results: Exenatide reduced (p<0.05) BMI-SDS (-0.09; -0.18, 0.00), % BMI 95th percentile (- 2.9%; -5.4, -0.3), weight (-3 kg; -5.8, -0.1), waist circumference (-3.2 cm; -5.8, -0.7), subcutaneous adipose tissue (-552 cm3; -989, -114), 2-hour-glucose during OGTT (-15.3 mg/dL; -27.5, -3.1), total cholesterol (11.6 mg/dL; -21.7, -1.5) and BMI (-0.83 kg/m²; -1.68, 0.01) without significant change in liver fat content (-1.36; -3.12, 0.4; p=0.06) in comparison to placebo. Safety and tolerability profiles were comparable to placebo with the exception of mild adverse events being more frequent in exenatide-treated patients. Conclusions: Treatment of adolescents with severe obesity with extended-release exenatide is generally well tolerated and leads to a modest reduction in BMI metrics and improvement in glucose tolerance and cholesterol. The study indicates that the treatment provides additional beneficial effects beyond BMI-reduction for the patient group