A 6-month randomized, double-blind, placebo-controlled trial of weekly exenatide in adolescents with obesity.

Weghuber, D; Forslund, A; Ahlström, H; Alderborn, A; Bergström, K; Brunner, S; Cadamuro, J; Ciba, I; Dahlbom, M; Heu, V; Hofmann, J; Kristinsson, H; Kullberg, J; Ladinger, A; Lagler, F B; Lidström, M; Manell, H; Meirik, M; Mörwald, K; Roomp, K; Schneider, R; Vilén, H; Widhalm, K; Zsoldos, F; Bergsten, P

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-month, 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) subcutaneous injections given once weekly. Oral glucose tolerance tests (OGTT) were conducted at the beginning and end of the intervention. RESULTS Exenatide reduced (P < .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 = .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.