Robert Avram
Endpoint critiqueInterventional / Structural Cardiology · Montreal Heart Institute
Orforglipron cut AHI, but the trial was one year, had no CV outcomes, and the effect is likely weight-driven.
X post ↗AHA 2026View all trials
Orforglipron for Obstructive Sleep Apnea
Vaishnavi KundelAtul MalhotraDaniel J. GottliebHolger WoehrleEllen B. DennehyGiulia CalamaiZhuqing LiuSujatro ChakladarRonan GrimesBeverly L. FalcónATTAIN-OSA InvestigatorsJuan José Morales VirgenMelchor Alpízar SalazarHsueh-Yu LiPablo CostanzoApinya VutikullirdThomas Sch uuml rholzRyutaro ShirahamaLuis LarrateguyGary SoucieKatharina LedererGuixia WangIwao GohmaXiaozhen JiangJohn HudsonKei NakamuraFrancisco Lopez MaldonadoCíntia CercatoLiang-Wen HangThomas SchaumLudger RoseXiaowei ZhuMauricio WaintrubMaria Arechavaleta GranellDiego AizenbergJianping YaoChu-Kuang ChouJames MaynardDirk WeberSaeko OsawaGaylon KippLuis Henrique CananiCesar Calvo VargasLuis NevárezLi LiPaul HartleyYan YangTetsuya KawanoKlaudia Halova KaroliovaJohn ParkerHanrong ChengCarolina CappellettiBryce PalchickJulia ChevtsDana MirallesBreno Balabem AlvesStacey LayleTereza HaasováZuzana Foglarova姜宏卫Gustavo AugustoMaria GrossmanJohannes HaasWasim HaqueAliu SanniPamela RossiLawrence SherKisria RechulYi-Ching YangLinong JiZongyou ChengJose Gerardo Gonzalez GonzalezBruno HalpernUlrike LenglerMarcos MayerDavid GreenZhifeng Cheng
What happened
Orforglipron reduces AHI by ~13 events per hour versus placebo in obstructive sleep apnea.
- MD -13.2
- 95% CI -17.7 to -8.7
- P<0.001
- n=712
Key points
- Context & question: Obstructive sleep apnea (OSA) is a common disorder characterized by repeated upper airway collapse during sleep that is associated with reduced quality of life and an increased incidence of cardiometabolic disease. The ATTAIN-OSA trials were conducted to assess the effects of orforglipron compared with placebo on moderate to severe OSA in adults with obesity or overweight.
- Methods & population: RCT, 1:1 randomization, Double-blind; 712 adults across two phase 3 trials (n=363 without PAP, mean age 48.4, 31.4% female; n=349 with PAP, mean age 51.1, 26.9% female) with moderate to severe OSA and BMI ≥27, followed for 52 weeks; Orforglipron vs Placebo; 52 weeks follow-up.
- Finding & limits: Orforglipron reduced the 52-week apnea-hypopnea index compared with placebo in patients without positive airway pressure and with positive airway pressure. Experts point out that the trial lasted only one year and had no cardiovascular outcomes, so heart benefit remains unproven. Whether the effect is anything more than weight loss is also unresolved.
Discussion
Expert perspectives 8
Ritu Thamman
Practice takeCardiac Imaging · University of Pittsburgh School of Medicine
Oral GLP1 orforglipron eased sleep apnea with or without Cpap, likely through weight loss, at $149/mo.
X post ↗Expert perspective
Vaishnavi Kundel6d ago
General · Mount Sinai Hospital
If approved to treat obstructive sleep apnea, orforglipron could be a promising oral pharmacologic option for people with overweight or obesity and this condition. A convenient daily pill may help expand access to treatment for sleep apnea, and it could potentially be used with CPAP or other therapies to better meet individual patient's needs.
ATTAIN-OSA co-authorShow 5 more perspectivesShow fewer perspectives
Expert perspective
Targeting the adverse #Cardiometabolic effects of #OSA esp #obesity has been challenging pre-GLPR-1As Today @AHAScience #ScientificSessions26 #LBT #ATTAIN-OSA provided the results from the first oral GLPR1A In addition to weight loss, reductions in blood pressure & inflammatory
t.coATTAIN-OSAExpert perspective
Martha Gulati6d ago
St.Martha's College Of Nursing
ATTAIN-OSA: 712 with excess weight + OSA... Orforglipron 🆚 placebo; 52wk AHI Δ vs placebo: −13.2/−12.0 events/h... Supportive for ⤵️ sleep apnea; CV benefit unproven
ATTAIN-OSAExpert perspective
Jen Can NuSH6d ago
🔔The ATTAIN-OSA paper and presentation are out. Orforglipron for the treatment of moderate to severe obstructive sleep apnea in patients with obesity. ▪️52 weeks, 2 different studies (with or without PAP therapy) Results (Treatment regimen estimand) ▪️Change in AHI: -17.8
t.coATTAIN-OSAExpert perspective
Mauricio Soto V6d ago
@AHAScience LIVE from #ScientificSessions26 @AHAScience ATTAIN-OSA: oral orforglipron in moderate-to-severe sleep apnea, 712 patients. About 18 fewer breathing events per hour vs 5 with placebo, and 10–11% weight loss at 1 year (JAMA). 3/6
t.coATTAIN-OSAExpert perspective
Martha Gulati9d ago
😴 ATTAIN-OSA at #AHA26 #ScientificSessions26 👥 712 adults with overweight/obesity + moderate–severe OSA 💊 Daily oral GLP-1 orforglipron vs placebo for 52 weeks 🫁 Separate trials: PAP users & those unable/unwilling to use PAP 🎯 Primary: change in apnea–hypopnea index Can
ATTAIN-OSAOutstanding questions
Open questions from this trial that would benefit from expert input.
Ask about this paper
Answers are grounded in this paper and cite their sources.
Full evidence
Why the trial, tables, limitations, PICO, abstract, media & sources
Full evidence
Why the trial, tables, limitations, PICO, abstract, media & sources
Why the trial?
Obstructive sleep apnea (OSA) is a common disorder characterized by repeated upper airway collapse during sleep that is associated with reduced quality of life and an increased incidence of cardiometabolic disease. The ATTAIN-OSA trials were conducted to assess the effects of orforglipron compared with placebo on moderate to severe OSA in adults with obesity or overweight.
Does once-daily oral orforglipron reduce the apnea-hypopnea index at 52 weeks compared with placebo in adults with moderate to severe obstructive sleep apnea and overweight or obesity?
View moreView less
Structured PICO
Does once-daily oral orforglipron reduce the apnea-hypopnea index at 52 weeks compared with placebo in adults with moderate to severe obstructive sleep apnea and overweight or obesity?
Population
712 adults across two phase 3 trials (n=363 without PAP, mean age 48.4, 31.4% female; n=349 with PAP, mean age 51.1, 26.9% female) with moderate to severe OSA and BMI ≥27, followed for 52 weeks.
Intervention
Orforglipron oral tablet once daily at maximum tolerated dose (equivalent to 9-, 14.5-, or 17.2-mg tablet dose) for 52 weeks
Comparator
Placebo once daily for 52 weeks (in patients either not receiving PAP in Trial 1 or receiving background PAP therapy in Trial 2)
Outcome
Change in apnea-hypopnea index (AHI, events/h) from baseline to week 52surrogate endpoint
Main Result
Mean Difference-13.2 (95% CI -17.7–-8.7)
Absolute Event Rate-17.8% vs -4.5%
p-valuep=<0.001
Once-daily oral orforglipron significantly reduces sleep-disordered breathing (AHI) by 12 to 13 events/h over 52 weeks compared with placebo in adults with moderate to severe OSA and overweight or obesity, regardless of background PAP therapy.
Where experts stand
GLP-1 receptor agonists evidence still formingExperts read this as a clear win for a daily pill that eases sleep apnea in people with excess weight, while cautioning that the benefit likely comes from weight loss and that heart benefit is unproven.
Clinicians accept that the pill lowered sleep apnea severity whether or not patients were using a breathing machine. Some see it as a convenient new option that could widen access to treatment, possibly alongside existing therapy. The open question is whether the benefit goes beyond weight loss and whether it leads to better heart outcomes over the longer term.
Agreement
Two cardiologists independently say the drop in sleep apnea severity is likely driven by weight loss rather than a separate effect of the drug.
2 clinicians say this directly
1 take classified by contention axis so far — the map appears as more land.
Still unclear
Experts point out that the trial lasted only one year and had no cardiovascular outcomes, so heart benefit remains unproven. Whether the effect is anything more than weight loss is also unresolved.
Implication
Offers oral GLP-1 option for moderate-to-severe OSA; extends class benefit to apnea-hypopnea index reduction.
Abstract
Importance: Obstructive sleep apnea (OSA) is a common disorder characterized by repeated upper airway collapse during sleep that is associated with reduced quality of life and increased incidence of cardiometabolic disease. Objective: To assess the effects of orforglipron on moderate to severe OSA in adults with obesity or overweight, compared with placebo. Design, Setting, and Participants: 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. Intervention: Patients were randomized (1:1) to receive either once-daily orforglipron (maximum tolerated dose: equivalent to 9-, 14.5-, or 17.2-mg tablet dose) or placebo. Main Outcomes and Measures: 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. Results: 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 (68.0%) 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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT06649045.
Cite This Study
Malhotra et al. (2026) conducted an RCT in Moderate to severe obstructive sleep apnea with obesity or overweight (n=712). Orforglipron vs. Placebo was evaluated on Change in apnea-hypopnea index (AHI, events/h) from baseline to week 52 (MD -13.2, 95% CI -17.7 to -8.7, p=<0.001).