Lilly’s Foundayo (orforglipron) reduced sleep apnoea severity and hypoxic burden in Phase 3 ATTAIN-OSA trials involving adults with obesity.
Written By: Aasritha Thippavajjala, PharmD
Reviewed By: Pharmacally Editorial Team
Lilly has reported positive Phase 3 results for Foundayo (orforglipron), demonstrating reductions in moderate-to-severe obstructive sleep apnoea (OSA) severity among adults with obesity or overweight. The findings from the two ATTAIN-OSA studies showed improvements in breathing interruptions and sleep-related oxygen deprivation in participants both using and not using positive airway pressure (PAP) therapy.
The results extend the clinical development of orforglipron beyond weight management and support further investigation of oral GLP-1 receptor agonists in obesity-associated conditions.
ATTAIN-OSA: Two Phase 3 Studies
The ATTAIN-OSA programme (NCT06649045) comprised two independent, randomised, double-blind, placebo-controlled Phase 3 studies involving 712 adults with obesity or overweight and moderate-to-severe OSA.
The first study enrolled 363 participants who were unable or unwilling to use PAP therapy, while the second included 349 participants who had used PAP for at least three months and intended to continue treatment. Both studies evaluated once-daily oral orforglipron against placebo over 52 weeks.
The primary endpoint was the change in the apnoea-hypopnoea index (AHI), which measures the number of breathing interruptions per hour of sleep. In the PAP study, participants temporarily discontinued PAP for seven days before sleep assessments to minimise the immediate treatment-related effects on AHI measurements.
Primary Endpoint: AHI Reductions in Both Populations
Under the primary treatment-regimen estimand analysis, orforglipron significantly reduced AHI compared with placebo at week 52.
In participants not using PAP, AHI decreased by 17.8 events per hour with orforglipron, compared with 4.5 events per hour with placebo. In the PAP study, reductions were 17.3 and 5.3 events per hour, respectively. Both between-group differences were statistically significant (P<0.001).
The additional efficacy-estimand analysis, which modelled outcomes assuming participants remained on assigned treatment, showed larger reductions. AHI decreased by 21.1 events per hour (43.8%) in the non-PAP study and 18.3 events per hour (27.5%) in the PAP study, compared with reductions of 4.3 (6.3%) and 5.5 events per hour (3.0%), respectively, with placebo.
These findings demonstrate improvements across both treatment settings, although the statistical estimates differ according to the analytical approach.
Secondary Endpoints: Hypoxic Burden and OSA Severity
Further analyses showed that 47.2% of participants not using PAP and 33.7% of those in the PAP study achieved at least a 50% reduction in AHI under the efficacy estimand.
The proportion achieving remission or mild OSA was 31.5% in the non-PAP study and 19.6% in the PAP study. Remission was defined as an AHI below five events per hour, while mild OSA required an AHI of 5 to below 15 events per hour without excessive daytime sleepiness.
Orforglipron also reduced sleep apnoea-specific hypoxic burden, which measures the depth and duration of oxygen deprivation associated with breathing disturbances. Reductions were 55.9% in the non-PAP study and 45.8% in the PAP study, compared with 18.3% and 17.0%, respectively, with placebo.
Weight Reduction and Cardiometabolic Findings
Participants receiving orforglipron also experienced substantial weight reduction. Under the efficacy estimand, average body weight decreased by 11.5% (12.7 kg) in the non-PAP study and 11.2% (12.8 kg) in the PAP study.
Additional findings included reductions in high-sensitivity C-reactive protein (hsCRP), a marker of inflammation, of 48.9% and 38.6%, respectively. Systolic blood pressure decreased by 8.6 mmHg in the non-PAP study and 7.3 mmHg in the PAP study.
However, these findings do not establish whether improvements in OSA resulted primarily from weight reduction or additional pharmacological effects.
Safety and Tolerability
Gastrointestinal adverse events, including nausea, diarrhoea, constipation, dyspepsia and vomiting, were the most frequently reported events and were generally mild to moderate.
Serious adverse events occurred in 8.8% of participants receiving orforglipron versus 4.9% receiving placebo in the non-PAP study. Corresponding rates in the PAP study were 6.2% and 5.2%.
Adverse events leading to treatment discontinuation occurred in 12.2% versus 3.8% in the non-PAP study and 6.8% versus 0.6% in the PAP study, respectively.
Regulatory Outlook and Clinical Interpretation
Lilly plans to submit the ATTAIN-OSA findings to the US Food and Drug Administration (FDA) by the end of 2026, seeking an indication for moderate-to-severe OSA in adults with obesity or overweight. Orforglipron is not currently approved for OSA.
The findings position orforglipron as a potential oral pharmacological option in an area where PAP remains an established treatment. However, the studies do not demonstrate that it can replace PAP therapy.
The results also warrant consideration alongside Lilly’s Zepbound (tirzepatide), which received FDA approval for obesity-associated OSA in December 2024. Orforglipron’s oral formulation could offer an alternative administration route, although no head-to-head comparison has established differences in efficacy or safety.
The 52-week findings provide evidence of improvements in breathing interruptions, hypoxic burden and body weight. Nevertheless, the absence of longer-term follow-up, limited racial and ethnic diversity, and exclusion of patients with diabetes, BMI below 27 or mild OSA restrict the generalisability of the results. Further studies will be needed to establish the durability of benefits and the contribution of weight-independent mechanisms.
References
Eli Lilly and Company. Lilly’s Foundayo (orforglipron) significantly reduced obstructive sleep apnea severity, reinforcing its potential to improve health beyond weight loss. 9 November 2026.
JAMA. Orforglipron for Obstructive Sleep Apnea Results From 2 Randomized Clinical Trials (ATTAIN-OSA)
A Master Protocol for Orforglipron in Participants with Obstructive Sleep Apnea and Obesity or Overweight (ATTAIN-OSA) ClinicalTrials.gov.NCT06649045
American Heart Association. Daily, oral GLP-1 medication reduced episodes of sleep apnea in adults with excess weight. 9 November 2026.
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.