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.
ATTAIN-OSA is investigating whether oral orforglipron can serve as a more accessible treatment for moderate-to-severe obstructive sleep apnea in adults with obesity or overweight.
Where it sits
this study against the rest of the orforglipron (ly-3502970) corpusSummary and findings
The ATTAIN-OSA trial evaluates the efficacy and safety of oral orforglipron in adults with moderate-to-severe obstructive sleep apnea (OSA) and obesity or overweight. Participants are randomized to receive either orforglipron at maximum tolerated doses of 12, 24, or 36 mg or placebo for 52 weeks. The primary endpoint is the change in Apnea-Hypopnea Index (AHI) at Week 52.
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.
Background
Obstructive sleep apnea (OSA) is prevalent, yet treatment options are limited, particularly due to poor adherence to positive airway pressure (PAP) therapies. Existing studies, such as the SURMOUNT-OSA trials, indicate that other treatments may improve OSA severity but often involve barriers to administration. This study is significant as it investigates orforglipron, an oral glucagon-like-peptide-1 receptor agonist, as a potentially more accessible treatment option for adults with moderate-to-severe OSA.
Methods
ATTAIN-OSA is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial with two studies. Study 1 includes participants unable or unwilling to use PAP, while Study 2 includes those who use PAP after a washout period. Participants are assigned to either placebo or orforglipron at maximum tolerated doses (12, 24, or 36 mg) for 52 weeks, following a standardized dose escalation schedule. The primary outcome measure is the change in Apnea-Hypopnea Index (AHI) at Week 52.
Results
Not reported in abstract.
Interpretation
The trial aims to assess a new oral treatment option for OSA, which could address adherence issues associated with existing therapies. However, without reported results, it is unclear how orforglipron compares to existing treatments in terms of efficacy and safety. The absence of detailed findings limits the ability to evaluate the clinical significance of the proposed intervention.
Key findings
- 712 participants randomized to orforglipron or placebo (Study 1, n=363; Study 2, n=349).
- Maximum tolerated doses of orforglipron are 12, 24, or 36 mg.
- Primary endpoint is change in Apnea-Hypopnea Index (AHI) at Week 52.
Limitations
- Not reported results or statistical analyses.
- Study design ongoing; no outcomes available yet.
- Primary endpoint change in AHI not yet reported.