Glucagon: Repurposing a Hormone for Obesity and Type 2 Diabetes Treatment

Glucagon is traditionally known for its role in raising blood glucose, often considered a "foe" in type 2 diabetes due to its contribution to hyperglycemia. However, emerging research suggests that glucagon possesses beneficial metabolic effects beyond simple glucose regulation, including significant potential for weight loss and improved glucose control. This comprehensive IUPHAR review specifically explores the multifaceted actions of glucagon and its therapeutic potential in treating both obesity and type 2 diabetes.

The review highlights that glucagon, whether administered alone or as part of multi-agonists (e.g., GLP-1/glucagon co-agonists), can significantly improve a range of metabolic parameters. It actively promotes energy expenditure through thermogenesis and enhances satiety, leading to reduced food intake and subsequent weight loss. The most significant finding is that glucagon can induce substantial weight loss and improve glycemic control by leveraging its diverse receptor-mediated actions in the liver, brain, and adipose tissue, moving beyond its traditional role as solely a hyperglycemic hormone. Furthermore, studies indicate that glucagon agonism can lead to a notable decrease in hepatic steatosis (fatty liver) and a substantial improvement in insulin sensitivity, positioning it as a powerful therapeutic agent for metabolic dysfunction.