— Novel retatrutide worked in overweight, obese adults with and without type 2 diabetes
October 21, 2026 • 4 min read
Treatment with the novel triple agonist retatrutide improved obstructive sleep apnea (OSA) in adults with obesity or overweight regardless of type 2 diabetes, two parallel randomized clinical trials showed.
Mean reduction in apnea-hypopnea index (AHI) at 80 weeks was 24.4 and 21.9 events per hour more than with placebo with the 9 and 12 mg doses in the TRIUMPH-1-OSA trial among patients without type 2 diabetes and 14.4 and 15.1 events per hour more than with placebo, respectively, in the TRIUMPH-2-OSA trial among patients with type 2 diabetes.
All these differences in the primary endpoint met statistical significance, researchers led by Ronald Grunstein, MD, PhD, of the Woolcock Institute of Medical Research at Macquarie University in Sydney, reported in the New England Journal of Medicineopens in a new tab or window.
The findings on the triple agonist of the glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and glucagon receptors were presented at the Congress of the European Sleep Research Societyopens in a new tab or window in Maastricht, the Netherlands.
These effects were "similar to those associated with this degree of weight loss in meta-analyses of randomized, controlled trials and nonrandomized intervention studies; the present trial extends these findings to patients with type 2 diabetes treated with incretins, with similar results," the researchers noted.
The findings also appeared on par with the GLP-1 receptor agonist tirzepatide (Zepbound), which in 2024 became the first drug approved to treat OSAopens in a new tab or window.
In the SURMOUNT-OSAopens in a new tab or window trials among patients with moderate-to-severe OSA and obesity who did not have type 2 diabetes, tirzepatide cut AHI by 20.0-23.8 events per hour more than placebo at 52 weeks. Body weight reductions were 17.7-19.6%.
With retatrutide, mean body weight loss was 12.5-22.2% in TRIUMPH-1-OSA and 12.1-18.5% in TRIUMPH-2-OSA, compared with 4.8% and 5.6% with placebo, respectively.
"I think our expectation was, because it is a triple [agonist], that we would have had a more significant impact on the weight loss and subsequent AHI, but that wasn't the case," commented Mariam Louis, MD, of the University of Florida in Jacksonville and incoming chair of the CHEST Sleep Medicine Network.
"I don't think we can say that it is superior to the tirzepatide, but it certainly, based on this particular study, produced very similar results," said Louis.
"It would be a good thing for the patients to have more options in their management of OSA," because while continuous positive airway pressure (CPAP) remains the gold standard for treatment, not everyone can tolerate it, said Hoi Yee Kwan, MBChB, chief of respiratory medicine at Kowloon Hospital in Hong Kong, who was not involved in the trials.
Having an option for switching could also help nonresponders, 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.
Grunstein's two international phase III trials had been "nested within larger basket trials of once-weekly subcutaneous retatrutideopens in a new tab or window," with 243 participants in TRIUMPH-1-OSA and 448 in TRIUMPH-2-OSA. Both included adults with moderate-to-severe OSA (AHI ≥15 per hour) and a body mass index of at least 27 randomly assigned to double-blind treatment with retatrutide at a dose of 4, 9, or 12 mg or placebo.
Whereas SURMOUNT-OSA had a portion with PAP and one without it, both TRIUMPH-OSA trials included people who were unable or unwilling to receive PAP therapy or who had been receiving PAP therapy for at least 3 consecutive months but stopped it for the trial (about 30% of participants).
TRIUMPH-1-OSA excluded participants with type 2 diabetes, while TRIUMPH-2-OSA recruited those with an HbA1c of 6.5-10.5% on a stable antidiabetic medication regimen.
The primary and secondary endpoint analyses prespecified a hybrid-treatment estimand with "imputation of values related to intercurrent events associated with treatment failure and a treatment-policy strategy elsewhere," the researchers noted. Results were similar in intention-to-treat analysis.
In TRIUMPH-1-OSA, the proportion of patients with OSA remission -- as marked by an AHI under 5 events per hour or 5-14 per hour if their Epworth Sleepiness Scale score dropped to 10 points or lower -- was 26.3% in the lowest-dose group, 51.6% in the intermediate-dose group, 42.3% in the high-dose group, and 12.5% in the placebo group (P<0.001 for the two higher doses).
In TRIUMPH-2-OSA, those proportions were 24.3%, 39.5%, 38.9%, and 12.6%, respectively (P<0.001 for the two higher doses).
"It would be better if the number of patients that have an AHI less than 5 per hour could be a bit higher," Kwan said. "Because our aim is to bring the OSA back to normal, which is something that we could have achieved with CPAP, which is the target for us to achieve."
Safety was similar to what was seen in the overall TRIUMPH trials, with the most common adverse events being gastrointestinal.