3 Key Takeaways
Plain English Summary- 01Core Finding
Final follow-up occurred on July 30, 2026.
- 02Study Evidence
Tested in a randomized controlled trial (363 patients) at the Phase III stage.
- 03Practical Meaning
Large Phase III clinical evidence — long-term durability and rare subgroup effects remain under study.
What This Means for You
These results provide evidence for the potential use of oral orforglipron to improve sleep-disordered breathing in adults with moderate to severe OSA and obesity or overweight.
The Discovery
To assess the effects of orforglipron on moderate to severe OSA in adults with obesity or overweight, compared with placebo (inactive comparison treatment).
Two 52-week, Phase 3, multicenter, double-blind, placebo (inactive comparison treatment)-controlled randomized clinical trials were conducted at 66 sites in the US, Argentina, Brazil, China, Czech Republic, Germany, Japan, Mexico, and Taiwan. Adults with moderate to severe OSA and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 27 or higher were enrolled between November 11, 2024, and July 23, 2025. Final follow-up occurred on July 30, 2026. Trial 1 included patients not receiving positive airway pressure treatment and trial 2 included patients receiving positive airway pressure treatment.
The primary end point was change in apnea-hypopnea index (AHI, events/h) from baseline to week 52. Seven key multiplicity-controlled secondary end points included change in sleep apnea-specific hypoxic burden, the Patient-Reported Outcomes Measurement Information System Short Form Sleep-Related Impairment T-score, and high-sensitivity C-reactive protein.
A total of 363 patients were randomized in trial 1 (mean age, 48.4 years; BMI, 37.4; AHI, 50.7 events/h; 31.4% female) and 349 patients were randomized in trial 2 (mean age, 51.1 years; BMI, 38.6; AHI, 57.6 events/h; 26.9% female). For the treatment regimen estimand, in trial 1, the mean AHI change was -17.8 for orforglipron compared with -4.5 for placebo (difference, -13.2 [95% CI, -17.7 to -8.7]; P <.001) at 52 weeks. In trial 2, the mean AHI change was -17.3 for orforglipron and -5.3 for placebo (difference, -12.0 [95% CI, -17.1 to -6.9]; P <.001) at 52 weeks. Of 7 key secondary end points, 6 were statistically significant, favoring orforglipron. Gastrointestinal events were the most commonly reported adverse events, occurring in 123 participants randomized to receive orforglipron vs 68 (37.4%) randomized to receive placebo (inactive comparison treatment) in trial 1 and in 125 (70.6%) participants randomized to receive orforglipron vs 63 (36.6%) randomized to receive placebo in trial 2.
How It Works, Simply
This pharmacology research focuses on selective receptor binding & pharmacokinetic optimization. Researchers evaluated it using a randomized controlled trial (363 patients) at the Phase III stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Final follow-up occurred on July 30, 2026.
- 02Study Evidence
Tested in a randomized controlled trial (363 patients) at the Phase III stage.
- 03Practical Meaning
Large Phase III clinical evidence — long-term durability and rare subgroup effects remain under study.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Randomized controlled trial
Randomized controlled trial (363 patients) · Phase III
Biological Pathway & Modality
Selective receptor binding & pharmacokinetic optimization
Intervention: Orforglipron for Obstructive Sleep Apnea: Results From 2 Randomized Clinical Trials
Experimental Findings & Endpoints
To assess the effects of orforglipron on moderate to severe OSA in adults with obesity or overweight, compared with placebo.
Two 52-week, Phase 3, multicenter, double-blind, placebo-controlled randomized clinical trials were conducted at 66 sites in the US, Argentina, Brazil, China, Czech Republic, Germany, Japan, Mexico, and Taiwan. Adults with moderate to severe OSA and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 27 or higher were enrolled between November 11, 2024, and July 23, 2025.
Final follow-up occurred on July 30, 2026. Trial 1 included patients not receiving positive airway pressure treatment and trial 2 included patients receiving positive airway pressure treatment.
The primary end point was change in apnea-hypopnea index (AHI, events/h) from baseline to week 52. Seven key multiplicity-controlled secondary end points included change in sleep apnea-specific hypoxic burden, the Patient-Reported Outcomes Measurement Information System Short Form Sleep-Related Impairment T-score, and high-sensitivity C-reactive protein.
A total of 363 patients were randomized in trial 1 (mean age, 48.4 years; BMI, 37.4; AHI, 50.7 events/h; 31.4% female) and 349 patients were randomized in trial 2 (mean age, 51.1 years; BMI, 38.6; AHI, 57.6 events/h; 26.9% female). For the treatment regimen estimand, in trial 1, the mean AHI change was -17.8 for orforglipron compared with -4.5 for placebo (difference, -13.2 [95% CI, -17.7 to -8.7]; P <.001) at 52 weeks.
In trial 2, the mean AHI change was -17.3 for orforglipron and -5.3 for placebo (difference, -12.0 [95% CI, -17.1 to -6.9]; P <.001) at 52 weeks. Of 7 key secondary end points, 6 were statistically significant, favoring orforglipron.
Gastrointestinal events were the most commonly reported adverse events, occurring in 123 participants randomized to receive orforglipron vs 68 (37.4%) randomized to receive placebo in trial 1 and in 125 (70.6%) participants randomized to receive orforglipron vs 63 (36.6%) randomized to receive placebo in trial 2.
Clinical Translation & Practice Context
These results provide evidence for the potential use of oral orforglipron to improve sleep-disordered breathing in adults with moderate to severe OSA and obesity or overweight.
The Bottom Line · Clinical Pearl
“These results provide evidence for the potential use of oral orforglipron to improve sleep-disordered breathing in adults with moderate to severe OSA and obesity or overweight.”
Published in JAMA · Current Stage: Phase III