ATTAIN-OSA Phase 3 Trial Investigates Oral Orforglipron for Moderate-to-Severe Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a highly prevalent and debilitating sleep-related breathing disorder strongly linked to obesity and significant cardiometabolic morbidity. Current first-line treatment, continuous positive airway pressure (CPAP), often suffers from poor long-term adherence due to discomfort and inconvenience, limiting its overall effectiveness. Injectable therapies, while showing promise (e.g., tirzepatide in SURMOUNT-OSA), introduce accessibility and adherence barriers. Orforglipron, an oral glucagon-like peptide-1 receptor (GLP-1R) agonist, offers a potentially more feasible and acceptable therapeutic option by targeting weight loss and potentially direct effects on upper airway function, addressing a critical unmet need in OSA management.

The ATTAIN-OSA program comprises two multicenter, randomized, double-blind, placebo-controlled Phase 3 trials enrolling 712 adults with moderate-to-severe OSA and obesity or overweight. Study 1 (n=363) includes participants unable or unwilling to use PAP, while Study 2 (n=349) involves PAP users who undergo a protocol-mandated washout before baseline polysomnography. Participants are randomly assigned to either placebo or an orforglipron capsule formulation at a maximum tolerated dose (12, 24, or 36 mg) for 52 weeks, following a standardized dose escalation schedule. The primary endpoint is the change in Apnea-Hypopnea Index (AHI) at Week 52.

The ATTAIN-OSA trials are designed to measure the efficacy and safety of orforglipron over 52 weeks in adults with moderate-to-severe OSA. The primary endpoint is the change in Apnea-Hypopnea Index (AHI) at Week 52, a crucial measure of OSA severity. Key secondary endpoints include sleep apnea-specific hypoxic burden, Patient-Reported Outcomes Measurement Information System sleep-related impairment, high-sensitivity C-reactive protein (hs-CRP), and changes in body weight. Other AHI-related endpoints will also be assessed to provide a comprehensive understanding of orforglipron's impact on OSA and associated metabolic markers. The study aims to demonstrate that orforglipron can significantly reduce AHI compared to placebo, offering a novel therapeutic pathway for patients struggling with OSA and its comorbidities. The inclusion of body weight as a secondary endpoint acknowledges the strong link between obesity and OSA pathogenesis, suggesting a multi-faceted benefit. The trial's design also allows for the evaluation of orforglipron's effect on systemic inflammation, as indicated by hs-CRP levels, which are often elevated in OSA patients. This comprehensive set of endpoints is intended to capture both the direct impact on breathing disturbances and broader health improvements. These results are pending completion of the trials.