Eli Lilly and Company’s investigational triple hormone receptor agonist retatrutide delivered substantial weight loss and meaningful relief from osteoarthritis pain in the Phase 3 TRIUMPH-4 trial, the company reported today. Retatrutide met all co-primary and key secondary endpoints at 68 weeks, underscoring its potential as a next-generation therapy for obesity with comorbid knee osteoarthritis.
In the global, randomized, double-blind study, adults with obesity or overweight (84% with a baseline BMI ≥35 kg/m²) and knee osteoarthritis received once-weekly retatrutide at 9 mg or 12 mg or placebo, alongside diet and physical activity. At the highest dose, average body weight reduction reached 28.7%, or approximately 71.2 lb, compared with minimal change in the placebo group. At the same time, retatrutide reduced WOMAC pain scores by up to 75.8% and improved physical function, with more than 1 in 8 patients reporting no knee pain at 68 weeks.
Retatrutide’s mechanism activates three hormone receptors — GLP-1, GIP and glucagon — distinguishing it from current dual- or single-agonist approaches and potentially enhancing weight-loss efficacy versus existing treatments.
Secondary analyses showed reductions in cardiovascular risk markers including non-HDL cholesterol, triglycerides and high-sensitivity C-reactive protein (hsCRP), and a systolic blood pressure reduction of about 14 mmHg at the highest dose.