Dual GLP-1/Glucagon Receptor Agonist: MEDI0382's Impact on Weight Loss and Metabolic Control in Rodents and Non-Human Primates

The study aimed to examine the effects of a peptide called MEDI0382, which acts on both GLP-1 and glucagon receptors. In the lab, MEDI0382 was tested for its capacity to increase cAMP levels in cells with GLP-1 or glucagon receptors, to enhance insulin production in response to glucose, and to stimulate glucose release from liver cells. Additionally, it was assessed for its impact on body weight, energy balance, and blood glucose levels in mice and monkeys through daily injections over a period of up to two months.

The results showed that MEDI0382 was effective in activating receptors in rodents, monkeys, and humans, with a preference for GLP-1 receptors. It led to significant weight loss in mice and was comparable to the GLP-1 analogue liraglutide in terms of glucose control. The weight loss effect was attributed to an increase in energy expenditure due to glucagon receptor activation and a decrease in food intake due to GLP-1 receptor activation. The weight loss effect was also observed in monkeys.

In conclusion, the repeated use of MEDI0382 resulted in significant weight loss and improved glucose control in both mice and non-human primates. It also reduced liver fat and levels of fasting insulin and glucose. The dual action on GLP-1 and glucagon receptors is deemed beneficial for managing weight and glucose in overweight or obese Type 2 diabetes patients.