Investigational drug retatrutide cut sleep apnea events in two phase 3 trials

What the study did

Retatrutide is an investigational once-weekly injection that activates three hormone receptors at once: GIP, GLP-1 and glucagon. Researchers ran two double-blind, randomized, placebo-controlled phase 3 trials nested inside Eli Lilly’s larger TRIUMPH program. TRIUMPH-1-OSA enrolled 243 adults without type 2 diabetes and TRIUMPH-2-OSA enrolled 448 adults with type 2 diabetes. All had moderate-to-severe obstructive sleep apnea and a BMI of at least 27.

Participants received retatrutide at 4, 9 or 12 mg, or placebo. The main outcome was the change in the apnea-hypopnea index (AHI), the average number of breathing pauses and shallow breaths per hour of sleep, after 80 weeks.

What it found

People started with severe apnea, averaging 58.6 and 55.9 events per hour. In TRIUMPH-1-OSA, the 9 mg and 12 mg doses lowered AHI by 24.4 and 21.9 more events per hour than placebo. In TRIUMPH-2-OSA, among people with diabetes, the differences were 14.4 and 15.1 events per hour. Results were similar in the intention-to-treat analysis.

Average weight loss ranged from 12.5% to 22.2% in the first trial and 12.1% to 18.5% in the second, compared with 4.8% and 5.6% on placebo. Gastrointestinal side effects were the most common adverse events.

What it does not prove

The trials measured breathing during sleep and body weight. They were not designed to show fewer heart attacks, strokes or deaths, or longer life. Much of the benefit likely reflects weight loss, so it is not clear whether the drug helps apnea in other ways. Many participants still had apnea at the end of treatment, and the trials were funded by the drug’s maker. Long-term safety beyond 80 weeks remains unknown.

The Youthful take

Sleep is one of the quiet pillars of healthspan, and sleep apnea is common and underdiagnosed in midlife. These are strong, well-designed trials, and they add to the evidence that treating excess weight can improve sleep breathing. Retatrutide is investigational, not approved by the FDA, and should not be sought outside a clinical trial. Anyone who snores heavily or wakes unrefreshed should talk with a physician about a proper sleep evaluation, because proven treatments already exist.