BACKGROUND: Retatrutide, an investigational triple agonist of glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors, may be useful for treating obstructive sleep apnea (OSA).
METHODS: In two phase 3, double-blind, randomized, placebo-controlled trials nested within larger basket trials of once-weekly subcutaneous retatrutide, we assigned adults with moderate-to-severe OSA and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 27, without (TRIUMPH-1-OSA) or with (TRIUMPH-2-OSA) type 2 diabetes, to receive retatrutide (4, 9, or 12 mg) or placebo. The primary end point was the change in the apnea-hypopnea index (AHI, the average number of apneas and hypopneas per hour of sleep) at 80 weeks with 9 mg and 12 mg of retatrutide. For OSA-related end points, a hybrid-treatment estimand was applied, with a hypothetical strategy used for participants who had intercurrent events suggesting treatment failure and a treatment-policy strategy used elsewhere. We also report intention-to-treat (ITT) results.
RESULTS: A total of 243 participants underwent randomization in TRIUMPH-1-OSA and 448 in TRIUMPH-2-OSA. The baseline mean AHI was 58.6 and 55.9 events per hour, respectively, and the mean body weight was 119.6 and 115.9 kg. At 80 weeks, the mean changes in the AHI (hybrid-treatment estimand) with retatrutide in TRIUMPH-1-OSA were -22.9 (4 mg), -34.3 (9 mg), and -31.7 (12 mg) events per hour, versus -9.9 with placebo (difference vs. placebo, -13.0 [95% confidence interval {CI}, -23.0 to -3.0], -24.4 [95% CI, -34.1 to -14.7], and -21.9 [95% CI, -32.2 to -11.5], respectively). The changes with retatrutide in TRIUMPH-2-OSA were -19.2 (4 mg), -24.7 (9 mg), and -25.4 (12 mg) events per hour, versus -10.3 with placebo (difference vs. placebo, -8.9 [95% CI, -15.9 to -2.0], -14.4 [95% CI, -21.6 to -7.2], and -15.1 [95% CI, -22.5 to -7.7]). For the ITT estimand, the corresponding differences from placebo were -13.2 (95% CI, -22.6 to -3.9), -24.7 (95% CI, -34.1 to -15.3), and -22.5 (95% CI, -31.9 to -13.1) in TRIUMPH-1-OSA and -8.8 (95% CI, -15.8 to -1.7), -13.9 (95% CI, -21.3 to -6.6), and -15.0 (95% CI, -22.5 to -7.4) in TRIUMPH-2-OSA. The mean percent change in body weight with retatrutide (key secondary end point) was -12.5 to -22.2% in TRIUMPH-1-OSA and -12.1 to -18.5% in TRIUMPH-2-OSA, versus -4.8% and -5.6% with placebo (treatment-regimen estimand). The most common adverse events were gastrointestinal.
CONCLUSIONS: In adults with OSA and obesity or overweight with or without type 2 diabetes, retatrutide resulted in significantly greater decreases in the AHI than placebo. (Funded by Eli Lilly; TRIUMPH-1 and -2 ClinicalTrials.gov numbers, NCT05929066 and NCT05929079.).
| Specialty | Score |
|---|---|
| Special Interest - Obesity -- Physician | |
| Family Medicine (FM)/General Practice (GP) | |
| General Internal Medicine-Primary Care(US) | |
| Endocrine | |
| Internal Medicine | |
| Respirology/Pulmonology | Coming Soon... |
Another GLP1 (not commercially available) proves useful for the treatment of OSA. A disease-oriented outcome. If it becomes available, has benefits in patient-oriented outcomes, and is reasonably priced, it might be good to include on formularies.
Weight loss is beneficial for sleep apnea. Outcomes are surrogates for clinical outcomes. This study may impact reimbursement for use of this drug class, but is not likely to change practice: the drug class is already widely used.
This RCT finds that ritatrutide, a triple agonist of GLP-1/GIP/GCG receptors, significantly reduced weight and AHI in patients with moderate-to-severe OSA. We already know that weight loss, however achieved, can improve OSA, and these benefits have been shown previously with other incretins. This trial demonstrates that ritatrutide is another agent that has efficacy in this context.
A comprehensive assessment of the effect of a triple incretin on sleep apnoea conducted over 80 weeks. The medication results in significant improvement in OSA measurements and weight reduction. It appears to be a class effect rather than specific to this particular agent, and the improvement is due to weight loss rather than some other effect on sleep apnoea.
, McMaster University