Retatrutide is a single peptide that consists of 39 amino acids engineered from a GIP peptide backbone to stimulate GLP-1, GIP, and GCGRs
It is a triple glucagon hormone receptor agonist (GLP-1, GIP, and GCGR receptors).It has been shown to achieve a more than 17.5% mean weight reduction in adults without diabetes but with obesity or preobesity (overweight) during a phase 2 trial. In the trial, the participants who received the highest dose (12 mg) showed a mean weight reduction of 24.2% after 48 weeks.
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.
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