The ATTAIN-OSA phase 3 trial randomized 712 adults with moderate-to-severe obstructive sleep apnea and obesity or overweight to once-daily oral orforglipron or placebo for 52 weeks.
RCT (n=712)
double-blind
randomized
Yes
Does orforglipron improve Apnea-Hypopnea Index in adults with moderate-to-severe obstructive sleep apnea and obesity or overweight?
The ATTAIN-OSA trial is designed to evaluate the efficacy and safety of the once-daily oral GLP-1 receptor agonist orforglipron for treating moderate-to-severe obstructive sleep apnea in adults with obesity or overweight.
ABSTRACT 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
Malhotra et al. (Mon,) conducted a rct in moderate-to-severe obstructive sleep apnea (n=712). Orforglipron vs. Placebo was evaluated on change in Apnea-Hypopnea Index (AHI) at Week 52. The ATTAIN-OSA phase 3 trial randomized 712 adults with moderate-to-severe obstructive sleep apnea and obesity or overweight to once-daily oral orforglipron or placebo for 52 weeks.