MEDI0382, a GLP-1/Glucagon Receptor Dual Agonist, Enhances Leptin-Mediated pSTAT3 Induction in Key Neuronal Regions That Regulate Metabolism

MEDI0382 is a potent GLP-1 and glucagon receptor dual agonist peptide that decreases body weight of obese mice by reducing food intake and enhancing energy expenditure. Here we explored whether MEDI0382 may, in part, mediate its effects on metabolism by enhancing leptin action. Diet-induced obese mice were administered vehicle, MEDI0382 (10 nmol/kg; s.c., q.d.) or vehicle and pair-fed to MEDI0382-treated mice for 10 days (n=15-16/group). During this period MEDI0382 induced 11% body weight loss (p per se as a factor, these data support the notion that MEDI0382 may mediate its effects on body weight and glycemic control via enhancing central leptin action. Disclosure H. Jouihan: None. P. Barkholt: Employee; Self; Gubra. R. Gronlund: None. J. Trevaskis: Employee; Self; MedImmune. Stock/Shareholder; Self; AstraZeneca.