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TRIUMPH-4: Retatrutide Delivers Weight Loss, Knee Osteoarthritis Pain Relief Eli Lilly and Company has announced positive topline results from the phase 3 TRIUMPH-4 clinical trial assessing the safety and efficacy of the 2 largest investigational doses of retatrutide in adults with obesity or overweight and knee osteoarthritis, and without diabetes, as an adjunct to healthy diet and physical activity.1 According to a December 11, 2025, release from the Company, both the 9 mg and 12 mg doses of the first-in-class GIP, GLP-1, and glucagon triple hormone receptor agonist met all primary and key secondary endpoints, delivering significant weight loss and improvements in pain and physical function at 68 weeks using both the efficacy and treatment-regimen estimands.1 "People with obesity and knee osteoarthritis often live with pain and restricted mobility, and may eventually require total joint replacement," said Kenneth Custer , PhD, executive vice president and president, Lilly Cardiometabolic Health.1 "We are encouraged by the results of TRIUMPH-4, which highlight the powerful effect of retatrutide, a first-in-class triple agonist, on body weight, pain and physical function

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While this metabolic effect supports weight management, the primary driver of GLP-1mediated weight loss is reduced calorie intake rather than a substantial increase in energy expenditure