Retatrutide sleep apnea trials cut breathing pauses in Phase 3 NEJM report

New retatrutide sleep apnea data from two Phase 3 trials show that Eli Lilly's experimental triple hormone drug cut breathing interruptions during sleep, according to a paper in The New England Journal of Medicine. The trials cover 691 adults with moderate to severe obstructive sleep apnea and a body mass index of at least 27, followed for 80 weeks. Both higher doses beat placebo on the main measure, the paper reports. The drug has no FDA approval, and the authors say long term safety and heart outcomes are still unknown.

How the TRIUMPH OSA trials were built

The TRIUMPH OSA trials were double blind and placebo controlled, and each one sat inside a larger basket trial of retatrutide, according to the NEJM abstract. TRIUMPH 1 OSA enrolled 243 adults without type 2 diabetes. TRIUMPH 2 OSA enrolled 448 adults with the condition. Participants were assigned to one of three retatrutide dose levels or to placebo, and Medscape reported that all groups also received lifestyle counselling. The primary end point was the change in the apnea hypopnea index at 80 weeks for the two higher doses. That index counts apneas and hypopneas, meaning full and partial pauses in breathing, per hour of sleep. Ronald Grunstein of the Woolcock Institute of Medical Research in Sydney led the investigators, and Eli Lilly funded the work.

Disease at entry was severe. Mean index scores were 58.6 events per hour in the trial without diabetes and 55.9 in the trial with diabetes, the abstract states. For the sleep end points, the investigators used what they call a hybrid treatment estimand. In plain terms, people whose course suggested the drug had failed were handled with a hypothetical approach, while everyone else was analysed under the treatment they were assigned. Readers comparing this paper with other obesity studies should check which estimand each one reports, because the choice can shift the headline number. Our guide on how to read a weight loss trial headline explains why that matters. The table below sets out the main figures from both studies as reported.

Breathing pauses and body weight fell on the drug

In TRIUMPH 1 OSA, the index fell by 34.3 events per hour on the middle dose and 31.7 on the highest dose, against 9.9 on placebo, the paper reports. After subtracting the placebo effect, the gaps were 24.4 and 21.9 events per hour, and both were statistically significant. The lowest dose cut the index by 22.9 events. In TRIUMPH 2 OSA, where everyone had type 2 diabetes, the two higher doses lowered the index by 24.7 and 25.4 events per hour, compared with 10.3 on placebo, according to a Physicians Weekly summary. The authors concluded that the retatrutide sleep apnea effect beat placebo whether or not people had diabetes.

After subtracting the placebo effect, the gaps were 24.4 and 21.9 events per hour, and both were statistically significant.

Weight fell alongside breathing events. In TRIUMPH 1 OSA, people on retatrutide lost an average of 12.5% to 22.2% of body weight across doses, against 4.8% on placebo, according to reports on the paper. In TRIUMPH 2 OSA the range was 12.1% to 18.5%, against 5.6%. Fox News Digital reported that about 68% of treated participants saw their sleep apnea improve by more than half. Hypoxic burden, a measure of how deep and long the low oxygen spells run, fell by about 75% in people without diabetes and 65% in those with it. Stomach and gut complaints were the most common side effects, coverage of the trials said. Full adverse event tables appear in the journal article.

A Mayo Clinic coauthor points to heart risk factors

Virend Somers, a Mayo Clinic cardiologist and coauthor, told Fox News Digital he had expected a benefit but was surprised by the "magnitude of benefit in patients with type 2 diabetes." He pointed to falls in systolic blood pressure, LDL cholesterol, systemic inflammation and neck circumference. "In diabetics, blood pressure is a key determinant of future cardiovascular risk," he said. These are risk factors, not heart attacks or strokes prevented. According to Fox, the researchers listed the lack of FDA approval as a limitation and said more studies are needed to learn how the drug affects long term cardiovascular outcomes. Sleep apnea is linked with higher rates of heart attack, stroke, high blood pressure and atrial fibrillation, the outlet reported.

Somers also described changes in blood sugar. Insulin levels fell by more than half in participants without diabetes, he said. Among those with type 2 diabetes, about 40% moved to prediabetes and another 40% no longer met diabetes criteria, by his account. He linked most of the gains to weight loss. The condition resolved fully in about 25% of people without diabetes and 15% of those with it, according to Somers. Some participants used CPAP and some did not, and he said CPAP use generally fell during the study. The researchers stressed that patients should not stop CPAP or other prescribed care because of these results, Fox reported.

Tirzepatide already holds the first sleep apnea drug label

Retatrutide would not be the first drug for this condition. In December 2024 the FDA extended the Zepbound label to moderate to severe obstructive sleep apnea in adults with obesity, the first approval of any medicine for the disease. Tirzepatide, also a Lilly drug, acts on two hormone receptors. Retatrutide adds a third, glucagon, to the GIP and GLP 1 targets. The two have not been compared directly in sleep apnea, so the retatrutide sleep apnea figures cannot show which works better. Differences in trial length, populations and estimands make reading separate papers side by side unreliable. An earlier Phase 3 readout in knee osteoarthritis also showed large weight loss, as we reported in December 2025.

Retatrutide has no FDA approval. The FDA has warned that unauthorised versions are being illegally marketed and sold online for weight loss, Fox News reported. Products bought outside a prescription system carry no assurance of identity, purity or strength. The sources reviewed for this story do not say when Lilly plans to file the sleep data with regulators, and the wider TRIUMPH programme in obesity and related conditions is still running. Outside experts welcomed more options while noting gaps in care. Wendy Troxel, a RAND senior behavioural scientist not involved in the work, said CPAP remains the frontline treatment. She added that she hoped greater awareness of treatment options would lead more people to get screened.

Conclusion

The retatrutide sleep apnea trials show large, statistically significant drops in breathing pauses over 80 weeks, in people with and without type 2 diabetes, according to the NEJM paper. They do not show fewer heart attacks, they do not compare the drug with tirzepatide, and they do not support stopping CPAP. Long term safety data, a regulatory filing and any approval decision are the next steps to watch.