Semaglutide is a GLP-1 receptor agonist that mimics the natural hormone glucagon-like peptide-1, which is released after eating. It works by stimulating insulin secretion when glucose levels are elevated, suppressing glucagon release, slowing gastric emptying, and acting on appetite centers in the brain to increase satiety and reduce food intake. These mechanisms improve glycemic control and significantly support weight reduction by decreasing hunger and caloric consumption. Semaglutide is used for type 2 diabetes and chronic weight management, and is commonly prescribed in weekly injectable formulations. Clinical studies show substantial weight loss and improvements in cardiometabolic markers, making it a cornerstone therapy in obesity medicine and metabolic disease management.

Tirzepatide is a dual incretin receptor agonist that activates both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor. By targeting these two incretin pathways simultaneously, tirzepatide enhances insulin secretion, reduces glucagon levels, slows gastric emptying, and produces strong central appetite suppression. The addition of GIP receptor activity appears to amplify metabolic signaling, improve insulin sensitivity, and enhance fat metabolism, resulting in greater weight loss and glucose control compared with single-receptor GLP-1 therapies. Tirzepatide is available as a once-weekly injectable medication for type 2 diabetes and chronic weight management. Clinical trials have demonstrated some of the largest weight reductions seen with pharmacologic obesity therapy, along with significant improvements in metabolic markers.

Retatrutide is an investigational triple-hormone receptor agonist that targets GLP-1, GIP, and glucagon receptors simultaneously, representing the next generation of metabolic therapies. While GLP-1 and GIP receptor activation improve insulin secretion, satiety, and glucose control, the glucagon receptor component increases energy expenditure and fat oxidation, potentially raising metabolic rate while reducing appetite. This multi-receptor mechanism is designed to address both sides of energy balance—decreasing caloric intake and increasing energy expenditure. Early clinical trials have demonstrated substantial weight loss and improvements in cardiometabolic parameters, with some studies reporting weight reductions approaching those seen with bariatric procedures. Retatrutide is still undergoing clinical development and has not yet received full regulatory approval, but it represents a promising advancement in the treatment of obesity and metabolic disease.