Lilly’s next-gen obesity drug cuts sleep apnea, knee pain in Phase 3

Eli Lilly’s Retatrutide Cuts Sleep Apnea Severity 60% and Knee Pain 73% in Phase 3 Trial

Eli Lilly announced on Saturday that its experimental triple-receptor agonist retatrutide reduced the severity of moderate-to-severe obstructive sleep apnea by 60.6% and knee osteoarthritis pain by up to 73.1% in a late-stage clinical trial, broadening the case for the drug’s ability to treat obesity-related conditions beyond weight loss alone.prnewswire

The findings, drawn from the Phase 3 TRIUMPH-1 trial, were presented at the American Diabetes Association’s 86th Scientific Sessions in New Orleans. TRIUMPH-1 enrolled 2,339 participants and used a novel “basket trial” design that evaluated retatrutide for weight management alongside nested studies for sleep apnea and knee osteoarthritis.prnewswire

Beyond Weight Loss

In the sleep apnea cohort, retatrutide reduced the apnea-hypopnea index — a measure of breathing interruption events per hour — by up to 36.1 events per hour from a baseline of 58.6, corresponding to the 60.6% reduction. For knee osteoarthritis, the drug lowered pain scores on the WOMAC scale by up to 4.3 points from a baseline of 6.0.prnewswire

The weight loss results were also notable. Participants on the 12 mg dose lost an average of 70.3 lbs, or 28.3% of their body weight, over 80 weeks. Among those who continued to 104 weeks, weight loss reached 30.3% — a level typically associated with bariatric surgery.clinicaltrialsarena

Lilly already markets Zepbound, which targets two of the same hormone receptors, for both obesity and obstructive sleep apnea. Retatrutide adds a third target — the glucagon receptor — which Lilly believes accounts for the deeper weight loss and metabolic improvements.reuters

Safety Signals and What Comes Next

Adverse events were largely consistent with other incretin-based therapies, including nausea, diarrhea, and vomiting. However, the company reported dysesthesia — an abnormal tingling or burning sensation — in up to 12.5% of patients on the higher doses compared with 0.9% on placebo. Discontinuation rates due to adverse events reached 11.3% on the highest dose.prnewswire

Retatrutide remains investigational and has not received regulatory clearance. Lilly is conducting additional late-stage studies across indications including chronic low back pain, cardiovascular outcomes, and liver disease, with further readouts expected over the next year.fiercebiotech

“By addressing weight, glycemia and obesity-related complications together, these results highlight retatrutide’s potential across the cardiometabolic spectrum,” said Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health.prnewswire