Full TRIUMPH-1 Retatrutide Results, Including Knee Osteoarthritis and Sleep Apnea Data, Published in NEJM

The New England Journal of Medicine published TRIUMPH-1 online on September 29, 2026, the first full peer-reviewed report of Eli Lilly's Phase 3 trial of retatrutide, an investigational triple hormone receptor agonist, in adults with obesity. Lilly first disclosed topline weight-loss figures from the trial in a May 21, 2026 announcement and added results from two nested knee osteoarthritis and obstructive sleep apnea substudies in a June 6, 2026 announcement; the NEJM paper is the trial's first complete publication of that data with full statistical detail, including the specific weight, pain and breathing outcomes and the methods used to analyze them.

TRIUMPH-1 (ClinicalTrials.gov identifier NCT05929066) is an 80-week, randomized, double-blind, placebo-controlled Phase 3 trial that enrolled 2,339 adults with obesity or overweight and at least one weight-related health condition, who did not have type 2 diabetes. Participants were randomized to once-weekly subcutaneous retatrutide at 4 mg, 9 mg or 12 mg, or placebo. The trial included two nested subgroups: 574 participants with knee osteoarthritis, whose pain was tracked using the WOMAC pain scale (ranging from 1 to 10, with higher scores indicating worse pain), and 243 participants with obstructive sleep apnea, whose breathing was tracked using the apnea-hypopnea index (AHI), a measure of breathing interruptions per hour of sleep. Primary endpoints were percent change in body weight, change in WOMAC pain score in the osteoarthritis subgroup, and change in AHI in the sleep apnea subgroup, each comparing the 9 mg and 12 mg doses against placebo.

Under the trial's primary, intention-to-treat based analysis, average body weight fell 17.6% at 4 mg, 23.7% at 9 mg and 25.0% at 12 mg, compared with 3.9% on placebo, differences of 19.8 and 21.0 percentage points for the 9 mg and 12 mg doses versus placebo (p<0.001 for both). The most common adverse events were gastrointestinal. According to Lilly's June 6, 2026 announcement describing the same underlying data, nausea affected 28.6% to 42.4% of participants across the three retatrutide doses versus 14.8% on placebo, diarrhea 25.2% to 34.1% versus 13.5%, constipation 23.8% to 26.1% versus 10.9%, and vomiting 10.6% to 25.3% versus 4.8%; discontinuation due to adverse events ranged from 4.1% to 11.3% across doses versus 4.9% on placebo.

Among the 574 participants with knee osteoarthritis, WOMAC pain scores fell by 3.2, 3.5 and 3.6 points at the 4 mg, 9 mg and 12 mg doses, respectively, versus 1.9 points on placebo, under a hybrid-treatment estimand that counted discontinuation or non-adherence as treatment failure (differences of 1.6 and 1.8 points for 9 mg and 12 mg versus placebo, p<0.001 for both). Under an intention-to-treat analysis, the corresponding falls were 3.4, 3.9 and 4.1 points versus 2.5 points on placebo (differences of 1.4 and 1.6 points, p<0.001 for both).

Among the 243 participants with obstructive sleep apnea, the apnea-hypopnea index fell by 22.9, 34.3 and 31.7 events per hour at the three ascending doses, versus 9.9 events per hour on placebo, under the same hybrid-treatment estimand (differences of 24.4 and 21.9 events per hour for 9 mg and 12 mg versus placebo, p<0.001 for both). Under an intention-to-treat analysis, the corresponding falls were 22.8, 34.3 and 32.1 events per hour versus 9.6 events per hour on placebo (differences of 24.7 and 22.5 events per hour, p<0.001 for both).

"Obesity drives more than 200 downstream diseases, yet we treat conditions in silos," said Ania Jastreboff, M.D., Ph.D., a lead TRIUMPH-1 investigator and professor of medicine and pediatrics at Yale School of Medicine, in Lilly's June 6, 2026 announcement of the same results. "[Retatrutide] resulted in weight reduction with improvements in glycemia, osteoarthritis pain, and sleep apnea, with many reaching healthy-range weight and normal blood sugar," she said, referring to the broader retatrutide trial program that includes TRIUMPH-1.

Retatrutide remains investigational and has not been approved by the FDA, the European Medicines Agency, Australia's Therapeutic Goods Administration or any other regulator. Scientific American, reporting on the NEJM and concurrent Lancet publications on September 29, 2026, quoted Lilly chief scientific and product officer Daniel Skovronsky describing the combined results as a "new high-water mark for what's possible in terms of weight loss," while University of Michigan surgery and internal medicine professor Randy Seeley cautioned that very large, rapid weight loss carries risks such as micronutrient deficiencies. This report describes clinical trial results and is not treatment or dosing guidance.