Retatrutide, Eli Lilly’s investigational once-weekly injection, cut breathing interruptions in adults with obstructive sleep apnea and excess weight over 80 weeks in two phase 3 trials, TRIUMPH-1-OSA and TRIUMPH-2-OSA, published last week in The New England Journal of Medicine. The drug isn’t approved.
Both trials were double-blind and placebo-controlled. Researchers led by Ronald R. Grunstein, MD, PhD, of the Woolcock Institute of Medical Research and Macquarie University in Sydney, reported that Retatrutide treatment enabled more participants to have remission of OSA or mild OSA without excessive daytime sleepiness,
according to Medscape.
Two Trials Enroll 691 Adults, With a Sponsor Helping Run Them
TRIUMPH-1-OSA enrolled 243 participants without type 2 diabetes; TRIUMPH-2-OSA enrolled 448 with it, EMJ reported. All had moderate-to-severe OSA, and a body mass index of at least 27. AHI counts breathing pauses and shallow-breathing episodes per hour of sleep.
Participants got weekly subcutaneous retatrutide at 4, 9 or 12 mg, or placebo. The primary endpoint was AHI change from baseline to week 80 for the 9 and 12 mg doses. The drug acts on three hormone receptors: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon.
According to MedPage Today, the trials were nestled within larger basket trials of the drug.
Medscape reported.
Breathing Events Fall at 9 mg and 12 mg Doses
Outlets framed the AHI results differently.
| Trial | Dose | Raw AHI reduction (events/hour) | Placebo-adjusted (events/hour) |
|---|---|---|---|
| TRIUMPH-1-OSA (no diabetes) | 9 mg | 34.3 | 24.4 |
| TRIUMPH-1-OSA | 12 mg | 31.7 | 21.9 |
| TRIUMPH-2-OSA (diabetes) | 9 mg | 24.7 | 14.4 |
| TRIUMPH-2-OSA | 12 mg | 25.4 | 15.1 |
Placebo groups cut AHI by 9.9 events per hour without diabetes and 10.3 with it, per EMJ.
At the 9 mg dose, 51.6% of participants without diabetes reached remission or mild OSA without excessive daytime sleepiness, versus 12.5% on placebo. With diabetes, the figures were 39.5% and 12.6%, Medscape reported.
According to MedPage Today, the TRIUMPH-1-OSA rate stood at 26.3% for the lowest dose, 51.6% for the intermediate dose, 42.3% for the high dose, and 12.5% for placebo.
In TRIUMPH-1-OSA, people given retatrutide shed an average of 12.5–22.2% of their body weight, against 4.8% for those on placebo. Weight reductions in TRIUMPH-2-OSA ranged from 12.1–18.5%, versus 5.6% with placebo. Gizmodo noted the apnea benefit was smaller in people with diabetes, which the figures bear out.
Hypoxic burden fell by approximately 63%-75% at the 9-mg and 12-mg doses across the two trials compared with 26%-30% with placebo. Gastrointestinal adverse events, including diarrhea, nausea, and constipation, were most common and generally mild to moderate, EMJ reported.
Retatrutide Looks Similar to Tirzepatide, Not Clearly Better
Tirzepatide became the first drug approved to treat OSA in 2024. In the SURMOUNT-OSA trials among patients with moderate-to-severe OSA and obesity who did not have type 2 diabetes, it cut AHI by 20.0-23.8 events per hour more than placebo at 52 weeks, with body weight reductions of 17.7-19.6%, MedPage Today reported. The retatrutide figures come at 80 weeks, so the timepoints differ.
Louis, who is incoming chair of the CHEST Sleep Medicine Network, said that because retatrutide is a triple agonist, she expected a bigger effect on weight loss and subsequent AHI, but that wasn’t the case.
Sanjay R. Patel, a pulmonologist with expertise in obesity and OSA based in Pittsburgh, who wasn’t involved in the trials, noted that without head-to-head trials it’s not possible to know whether retatrutide offers any advantages over tirzepatide, Medscape reported.
Louis added. If they didn’t lose weight with, for example, the first generation GLP-1, maybe they’ll have better success with this one,
she said. Hoi Yee Kwan, MBChB, chief of respiratory medicine at Kowloon Hospital in Hong Kong, who wasn’t involved, said It would be a good thing for the patients to have more options in their management of OSA.
CPAP remains the gold standard, he noted, but not everyone tolerates it.
Clinicians Weigh CPAP After Weight Loss
If they feel well, a home sleep test would be reasonable before deciding next steps, he said. He reported consulting fees from Apnimed, SleepRes, Bayer Pharmaceuticals and Powell Mansfield, among other industry relationships.
We don’t want to miss residual OSA,
she said, noting that even mild disease can fragment sleep.
Approval Timing Stays Unanswered as Gaps Remain
EMJ stressed the drug remains investigational.
Gizmodo also noted that roughly a quarter of OSA cases aren’t tied to overweight, where weight-loss drugs are unlikely to do much. The sources don’t address durability after stopping the drug. Gurubhagavatula called for research into why weight loss improves OSA substantially in some patients but not others, and whether incretin-based drugs ease poor sleep or daytime sleepiness through mechanisms independent of weight loss.