Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials

作者：K. Giblin, Lee M. Kaplan, Virend Kristen Somers, Carel Wynand le Roux, David John Hunter, Qiwei Wu, Amy Lalonde, Nadia Y. Ahmad, Mary Angelyn Bethel · 发表于：Diabetes Obesity and Metabolism · 年份：2025 · DOI：10.1111/dom.70209 · 被引用次数：21 · 研究领域：Diabetes Treatment and Management、Obstructive Sleep Apnea Research、Bariatric Surgery and Outcomes

AIMS: Retatrutide, a novel synthetic molecule, is a triple agonist activating the glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 and glucagon receptors. The TRIUMPH clinical development program evaluates its safety and efficacy concurrently for the treatment of obesity and two related complications-obstructive sleep apnea (OSA) and knee osteoarthritis (OA). A novel basket trial design simultaneously evaluates retatrutide treatment across these multiple adiposity-related disease states. MATERIALS AND METHODS: TRIUMPH consists of four Phase 3, multicenter, randomized, double-blind studies assessing weekly subcutaneous retatrutide compared to placebo, in conjunction with healthy diet and physical activity in over 5800 participants. The four trials consist of two weight management basket trials (TRIUMPH-1 and TRIUMPH-2) with OSA and/or OA protocols nested within the weight management trial; one weight management trial in a population with CVD (TRIUMPH-3); and one stand-alone OA trial (TRIUMPH-4). The primary endpoint for weight management is percent change in body weight, for OSA is change in Apnea-Hypopnea Index and for knee OA includes change in the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale score. The basket trial permits independent analysis of weight management, OSA and OA studies with type I error rate controlled at α = 0.05, split between the overarching weight management and each basket trial. CONCLUSIONS: By recrui...