Reviews retatrutide's mechanism as a triple agonist targeting GLP-1, GIP, and glucagon receptors, and its synergistic effects on insulin secretion, glucose control, and appetite. Summarizes phase 1–3 data demonstrating substantial weight loss and glucose lowering. Notes GI adverse events as the main tolerability concern.
Abstract
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.
Authors
Abdul-Rahman, Toufik; Roy, Poulami; Ahmed, Fatma Kamal; Mueller-Gomez, Jann Ludwig; Sarkar, Sarmistha; Garg, Neil; Femi-Lawal, Victor Oluwafemi; Wireko, Andrew Awuah; Thaalibi, Hala Ibrahim; Hashmi, Muhammad Usman; Dzebu, Andrew Sefenu; Banimusa, Sewar Basheer; Sood, Aayushi