Retatrutide cuts sleep apnea events in two Phase 3 trials

Eli Lilly’s investigational drug retatrutide reduced breathing interruptions during sleep substantially more than placebo in two Phase 3 trials of adults with obstructive sleep apnea (OSA), according to results published online in the New England Journal of Medicine on October 21, 2026. The results were also presented at the 28th Congress of the European Sleep Research Society, held October 20 to 23.

The trials are TRIUMPH-1-OSA, in adults without type 2 diabetes, and TRIUMPH-2-OSA, in adults with it. The corresponding author is Ronald R. Grunstein of the Woolcock Institute of Medical Research in Sydney.

What the trials tested

Both were Phase 3, double-blind, randomized, placebo-controlled trials. Each was nested inside one of Lilly’s larger TRIUMPH basket trials of once-weekly retatrutide, which are registered on ClinicalTrials.gov as NCT05929066 (TRIUMPH-1) and NCT05929079 (TRIUMPH-2). Per Lilly’s summary, the sleep apnea studies had their own eligibility criteria, endpoints and analyses, while sharing the parent trials’ treatment design.

• TRIUMPH-1-OSA randomized 243 adults at 22 centers in 3 countries.
• TRIUMPH-2-OSA randomized 448 adults at 49 centers in 5 countries.

Everyone enrolled had moderate-to-severe OSA and a body-mass index of at least 27. Participants were assigned in equal numbers to one of three retatrutide dose levels or to placebo, for 80 weeks. Everyone also got lifestyle counseling. The main question was how much the two highest doses lowered the apnea-hypopnea index (AHI), a count of how often breathing stops or becomes shallow during each hour of sleep.

The patients started with severe disease. Mean baseline AHI was 58.6 events per hour in TRIUMPH-1-OSA and 55.9 in TRIUMPH-2-OSA. Thirty events an hour is the usual threshold for severe OSA, and roughly three-quarters of each group were above it.

What the results show

Under the trials’ main OSA analysis, the average AHI change at week 80 in TRIUMPH-1-OSA was:

• −22.9 events per hour at the lowest dose
• −34.3 at the middle dose
• −31.7 at the highest dose
• −9.9 with placebo

In TRIUMPH-2-OSA, the changes were −19.2, −24.7 and −25.4, against −10.3 with placebo.

Put another way, in TRIUMPH-1-OSA the middle dose removed about 24.4 more events an hour than placebo did. In TRIUMPH-2-OSA, where everyone had type 2 diabetes, the gap at the two highest doses was smaller, at 14.4 and 15.1. Weight loss was also smaller with diabetes. Body weight fell 12.5 to 22.2 percent across retatrutide doses in TRIUMPH-1-OSA and 12.1 to 18.5 percent in TRIUMPH-2-OSA, against 4.8 and 5.6 percent with placebo.

A stricter measure points the same way. In TRIUMPH-1-OSA, 51.6 percent of participants at the middle dose ended the trial with either no OSA or mild OSA without excessive daytime sleepiness, compared with 12.5 percent on placebo. The investigators wrote that in such participants, “PAP therapy may no longer be recommended,” referring to positive airway pressure machines such as CPAP.

Safety

Adverse events were common in every group. In TRIUMPH-1-OSA they were reported by 88 to 93 percent of retatrutide participants and 76 percent on placebo. In TRIUMPH-2-OSA the figures were 73 to 84 percent and 71 percent. Lilly’s summary says these events were mostly gastrointestinal, generally mild to moderate, and most frequent during dose escalation. The Limbic, a medical news outlet, reported that pulse rate rose with retatrutide, by a peak of 5 to 7 beats per minute across the trials.

Four deaths were reported across the two trials. Three were in placebo groups. One, from an upper gastrointestinal hemorrhage, was in a retatrutide group.

What is not known

• How long the effect lasts. The trials ran 80 weeks, plus a short follow-up period. They do not show what happens to sleep apnea if the drug is stopped.
• Whether it changes CPAP use. The authors say the effect of treatment on adherence to PAP therapy was not measured. Between 26 and 33 percent of each group was using PAP at baseline.
• How far the results generalize. The investigators note that participants had relatively mild sleep-related symptoms at the start. Most participants in both trials were Hispanic or Latino, between 69 and 85 percent of each treatment group in Lilly’s baseline table.
• The lowest dose. It was not part of the formal statistical testing hierarchy, so any significance reported for it is nominal, according to Lilly’s summary.
• Independence. Eli Lilly funded both trials. The Limbic reported that the company was involved in trial design, conduct, data analysis, interpretation, manuscript preparation and the decision to submit.

Why it matters

Retatrutide is an investigational triple agonist of the GIP, GLP-1 and glucagon receptors. It is not approved by the FDA for any use. These results come from TRIUMPH, the registrational trial program Lilly is running for the drug.

That matters because retatrutide is already sold widely outside that program. Products labeled as retatrutide are marketed online as “research peptides,” which drew FDA warning letters to two sellers this year. In Australia, New South Wales health data tied retatrutide to most peptide-linked emergency visits. The NEJM results describe a pharmaceutical-grade drug, given at controlled doses with medical monitoring, over 80 weeks. They say nothing about what is in a vial bought online.

What to watch

The next steps to look for are results from the other parts of the TRIUMPH program, and whether and when Lilly files retatrutide with the FDA, including for sleep apnea. Also watch whether longer follow-up shows what happens to sleep apnea after treatment ends.

Amino Wire does not give medical advice.