Evaluating the Sub-chronic Effects of MEDI0382, a GLP-1/Glucagon Receptor Dual Agonist, on Weight Loss in Male ob/ob Mice

MEDI0382, a balanced GLP-1/glucagon dual receptor agonist, is under development for the treatment of type 2 diabetes (T2DM). MEDI0382 reduces food intake and improves glucose control in lean and obese mice. Here, we determined the effects of MEDI0382 on body weight in leptin-deficient ob/ob mice. MEDI0382 (10, 20 or 30 nmol/kg), liraglutide (30 nmol/kg; a GLP-1 analog), or G1437 (30 nmol/kg; a lipidated glucagon receptor agonist) was administered to ob/ob mice for 21 days. Body weight was reduced by MEDI0382 treatment compared to vehicle controls, with 15% weight loss observed in the highest dose group. In comparison, liraglutide reduced body weight by 8% and G1437 by 29% (both p