Orforglipron for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity or overweight: Study design and baseline characteristics of ATTAIN-OSA, a phase 3 trial.

INTRODUCTION: Obstructive sleep apnea (OSA) is highly prevalent, yet current treatment remains limited. Poor adherence to positive airway pressure (PAP) and barriers associated with injectable therapies can limit potential therapeutic options for moderate-to-severe OSA. The SURMOUNT-OSA trials demonstrated that tirzepatide contributes to OSA severity improvements; however, the injectable mode of administration introduces barriers that may limit accessibility and long-term adherence. Orforglipron, a once daily oral glucagon-like-peptide-1 receptor agonist, may offer a more feasible and accepted therapeutic option. ATTAIN-OSA was developed to evaluate the efficacy and safety of oral orforglipron in adults with moderate-to-severe OSA. METHODS: ATTAIN-OSA is a master protocol with two multicenter, randomized, double-blind, placebo-controlled Phase 3 trials enrolling adults with moderate-to-severe OSA and obesity or overweight. Study 1 includes participants unable or unwilling to use PAP. Study 2 includes participants who use PAP and complete a protocol-mandated washout before baseline polysomnography. Participants are randomly assigned to placebo or orforglipron capsule formulation at maximum tolerated dose (12, 24, or 36 mg) for 52 weeks following a standardized dose escalation schedule. RESULTS: The primary endpoint is change in Apnea-Hypopnea Index (AHI) at Week 52. Key secondary endpoints include sleep apnea-specific hypoxic burden, Patient-Reported Outcomes Measurement Information System sleep-related impairment, high-sensitivity C-reactive protein, and body weight, and other AHI-related endpoints. Overall, 712 participants have been randomized to orforglipron or placebo (Study 1, n = 363; Study 2, n = 349). CONCLUSION: ATTAIN-OSA evaluates if once-daily oral orforglipron can provide an effective and more accessible therapeutic approach to treat moderate-to-severe OSA in adults with obesity or overweight. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06649045.