Once-daily oral orforglipron improved moderate to severe obstructive sleep apnea (OSA) compared with placebo in adults with obesity or overweight, based on findings from the ATTAIN-OSA trial presented at AHA 2026 and simultaneously published in JAMA.

Researchers randomized 363 patients from 66 sites in the U.S., Argentina, Brazil, China, Czech Republic, Germany, Japan, Mexico, and Taiwan to either once-daily orforglipron (maximum tolerated dose: equivalent to 9-, 14.5-, or 17.2-mg tablet dose) or placebo. All participants had severe OSA and a BMI of 27 or higher and were divided into two separate trials based on whether they were receiving positive airway pressure treatment or not.

The primary endpoint was change in apnea-hypopnea index (AHI, events/h) from baseline to 52 weeks. Overall, orforglipron significantly improved the mean change in AHI (events/h) compared with placebo at 52 weeks (−17.8 vs. −4.5 for patients not receiving positive airway pressure treatment (CPAP); −17.3 vs. −5.3 for patients receiving CPAP treatment).

"Even a modest decrease in blood pressure can help protect a patient's heart and overall health," said Vaishnavi Kundel, MD, MSc, in presenting the findings. "Previous research has confirmed that using CPAP devices while sleeping can help lower blood pressure by about two to three points. In these studies, blood pressure fell by about seven points after one year of taking this oral GLP-1 medication. That's a meaningful blood pressure change that would have a positive impact on cardiovascular health for people with sleep apnea."

In other findings, breathing interruptions during sleep decreased by about 18 events per hour among participants taking orforglipron, compared with about 5 events per hour among participants taking a placebo in both trial arms. In addition, treatment with orforglipron led to greater reductions in sleep apnea-related drops in blood oxygen levels compared with placebo in both studies.

Researchers also observed a decrease in body weight by about 10-11% among participants in the groups taking orforglipron compared with only 1-2% in the placebo groups, respectively, and blood tests showed a larger reduction in the inflammation marker high-sensitivity C-reactive protein (hs-CRP) among people assigned to orforglipron. The most common side effects were nausea, diarrhea and constipation and were self-reported by participants as mostly mild to moderate.

Moving forward, Kundel et al., note that future studies are needed to explore if other potential mechanisms beyond weight loss contributed to the benefits found in people taking orforglipron or other GLP-1 medications.

Clinical Topics: Heart Failure and Cardiomyopathies, Heart Failure and Cardiac Biomarkers, Sleep Apnea

Keywords: AHA Annual Scientific Sessions, AHA26, Sleep Apnea Syndromes, Sleep Apnea, Obstructive, Glucagon-Like Peptide 1, Body Mass Index, C-Reactive Protein, Blood Pressure, Obesity