The power of three: Retatrutide's role in modern obesity and diabetes therapy

The increasing prevalence of obesity and type 2 diabetes mellitus has resulted in a significant challenge to public health throughout the globe. It required the development of novel therapeutic approaches. Retatrutide is a groundbreaking triple agonist that targets glucagon receptors, gastric inhibitory polypeptide, and glucagon-like peptide-1. Retatrutide's complex mechanism of action involves a synergistic interaction among these receptors, resulting in increased insulin secretion, improved glucose homeostasis, and refined appetite modulation. Clinical trials in phases 1 to 3 have demonstrated significant efficacy, highlighted by significant reductions in body weight and favorable glycemic control outcomes. Additionally, retatrutide shows promise in mitigating cardiovascular risk factors and addressing metabolic dysfunction-associated steatotic liver disease. However, careful attention is required to delineate its long-term safety profile, explore its potential in special populations, unravel its adjunctive therapeutic roles, and elucidate its mechanisms in pediatric cohorts. As a transformative therapeutic modality, retatrutide represents a beacon of hope, signifying transformative changes in the management landscape of obesity and type 2 diabetes mellitus (T2DM), and warranting continued exploration and refinement in clinical practice. This narrative review examines the therapeutic potential of retatrutide in the management of obesity and T2DM. [Display omitted] •Innovative Mechanism of Action: Retatrutide is a groundbreaking triple agonist targeting glucagon receptors, gastric inhibitory polypeptide, and glucagon-like peptide-1, synergistically enhancing insulin secretion, improving glucose homeostasis, and refining appetite modulation.•Significant Clinical Effectiveness: Clinical trials (phases 1 to 3) demonstrate retatrutide's substantial efficacy, evidenced by notable reductions in body weight and improved glycemic control outcomes, marking it as a promising therapeutic for obesity and type 2 diabetes mellitus.•Broad Therapeutic Potential: Beyond glycemic control and weight reduction, retatrutide shows promise in mitigating cardiovascular risk factors and addressing non-alcoholic fatty liver disease, expanding its potential impact on metabolic health.•Focus on Safety and Special Populations: Ongoing research is essential to delineate retatrutide's long-term safety profile, explore its potential in special populations, and elucidate its mechanisms i