Once-weekly treatment with the triple agonist retatrutide helps improve obstructive sleep apnoea (OSA) in adults with obesity or overweight with or without type 2 diabetes (T2D), according to the phase III TRIUMPH-1-OSA and TRIUMPH-2-OSA studies.
From baseline to week 80, the Apnoea-Hypopnoea Index (AHI) decreased by a mean of 22.9 events/h with retatrutide 9 mg and 31.7 events/h with 12 mg vs 9.9 events/h with placebo in the no-diabetes population in TRIUMPH-1-OSA (p<0.001 for both comparisons). [N Engl J Med 2026;doi:10.1056/NEJMoa2611477]
In the T2D population in TRIUMPH-2-OSA, the mean change in AHI at 80 weeks was −24.7 events/h with retatrutide 9 mg and −25.4 events/h with 12 mg vs −10.3 events/h with placebo (p<0.001 for both comparisons).
“The treatment effect on the AHI appeared consistent across prespecified subgroups, including subgroups defined according to use of positive airway pressure (PAP) therapy,” said first author Dr Ronald Grunstein from the Woolcock Institute of Medical Research, Macquarie Park, New South Wales, Australia, and colleagues.
Retatrutide-treated participants lost a greater percentage of their body weight compared with those who received placebo: from −12.5 percent to −22.2 percent vs −4.8 percent in TRIUMPH-1-OSA and from −12.1 percent to −18.5 percent vs −5.6 percent in TRIUMPH-2-OSA.
Grunstein and colleagues noted that retatrutide also led to significantly greater reductions in other measures of sleep-disordered breathing.
“Retatrutide treatment enabled more participants to have remission of OSA or mild OSA without excessive daytime sleepiness; in such participants, PAP therapy may no longer be recommended,” they said.
Furthermore, hypoxic burden was substantially reduced in retatrutide-treated participants, which indicated that less cumulative hypoxaemia was associated with respiratory events, according to Grunstein and colleagues, who also acknowledged the need for prospective studies to determine whether this reduction in hypoxic burden translate into improved long-term cardiovascular outcomes.
TRIUMPH-OSA trials
Grunstein and colleagues noted that the two TRIUMPH-OSA trials were nested within larger basket trials of once-weekly subcutaneous retatrutide. The trials involved adults with moderate-to-severe OSA and a BMI of ≥27 kg/m2 with or without T2D.
Participants were randomly assigned to receive retatrutide at 4, 9, or 12 mg or placebo. The primary endpoint was the change in the AHI at 80 weeks with 9 and 12 mg of retatrutide.
TRIUMPH-1-OSA included 243 participants without T2D (average age 47 years, 36.6 percent female, 53 percent White), including 181 in the retatrutide groups and 62 in the placebo group. At baseline, the mean AHI was 58.6 events/h, and the mean body weight was 119.6 kg.
TRIUMPH-2-OSA included 448 participants with T2D (average age 54 years, 40 percent female, 51.1 percent White), including 335 in the retatrutide groups and 113 in the placebo group. At baseline, the mean AHI was 55.9 events/h, and the mean body weight was 115.9 kg.
At week 80, more participants in the retatrutide group vs the placebo group achieved a ≥50-percent decrease in AHI (TRIUMPH-1-OSA: 61.4 percent to 65.7 percent vs 23.9 percent; TRIUMPH-2-OSA: 52.3 percent to 52.5 percent vs 24.4 percent) and an AHI of <5 or 5–14 events/h with Epworth Sleepiness Scale score of ≤10 (TRIUMPH-1-OSA: 42.3 percent to 51.6 percent vs 12.5 percent; TRIUMPH-2-OSA: 38.9 percent to 39.5 percent vs 12.6 percent).
The percent change in sleep apnoea–specific hypoxic burden was –70.2 percent to –75 percent with retatrutide vs –25.5 percent with placebo in TRIUMPH-1-OSA and –62.8 percent to –64.1 percent vs –30 percent, respectively, in TRIUMPH-2-OSA.
“The effects of retatrutide at a dose of 4 mg did not reach statistical significance under the testing hierarchy in either trial for these endpoints,” Grunstein and colleagues noted.
Adverse events (AEs) occurred in 88 percent to 93 percent of retatrutide recipients and 76 percent of placebo recipients in TRIUMPH-1-OSA and 73 percent to 84 percent of retatrutide recipients and 71 percent of placebo recipients in TRIUMPH-2-OSA. The most common AEs were gastrointestinal, including diarrhoea, nausea, constipation, and dyspepsia, and were generally mild to moderate.
Serious AEs occurred in 8 percent in the retatrutide groups and 10 percent in the placebo group in both TRIUMPH-1-OSA and TRIUMPH-2-OSA. One participant in TRIUMPH-2-OSA died during receipt of retatrutide at the 9-mg dose, and three participants died during receipt of placebo in TRIUMPH-1-OSA (n=2) and TRIUMPH-2-OSA (n=1).