Retatrutide is a single peptide that acts on three hormonal pathways involved in metabolism:

1. GLP-1 receptor agonism: By activating glucagon-like peptide-1 receptors, it increases insulin secretion in response to meals, decreases appetite (through brain satiety centers), and slows stomach emptying. This leads to lower food intake and better post-meal blood sugar profiles, similar to medications like Semaglutide.
2. GIP receptor agonism: Stimulating the glucose-dependent insulinotropic polypeptide receptor further enhances insulin release and may have synergistic effects on weight loss when combined with GLP-1 activation. GIP agonism can also support fat metabolism and insulin sensitivity.
3. Glucagon receptor agonism: Uniquely, Retatrutide also mildly activates glucagon receptors, which increases energy expenditure by promoting lipolysis (fat breakdown) and thermogenesis in the liver and adipose tissue. While glucagon typically raises blood sugar, in the presence of GLP-1/GIP agonism the net effect is balanced to favor fat burning without hyperglycemia.

These combined actions make Retatrutide a powerful agent for weight loss and metabolic improvement. Essentially, it delivers the benefits of GLP-1 agonists (like appetite suppression and insulin enhancement) with added fat-burning and calorie-expending properties from the glucagon receptor stimulation. Patients on Retatrutide experience reduced hunger, eat less, and simultaneously their bodies are nudged to burn more calories. Over weeks, this results in substantial fat loss. Additionally, by improving insulin sensitivity and glycemic control, Retatrutide helps lower HbA1c (average blood sugar) and may reduce risks of diabetic complications. Non-alcoholic fatty liver disease markers also improve as the compound encourages usage of liver fat as fuel.