1376 An Unprecedented 94% Reduction in AHI with Semaglutide in a CPAP-Intolerant Patient

Abstract Introduction Severe obstructive sleep apnea (OSA) with AHI >100/hr and coexisting sleep-related hypoventilation is rarely reversible without PAP therapy or bariatric surgery. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve weight and metabolic status, but near-complete remission of very severe OSA using pharmacologic therapy alone remains uncommon. This case describes dramatic improvement in OSA severity and hypercapnic physiology in a PAP-intolerant patient after substantial weight loss with semaglutide. Report of case(s) A 65-year-old man with obesity, COPD, diabetes, hyperlipidemia, anxiety, and a 90 pack-year smoking history underwent baseline polysomnography (PSG) in 2021 for snoring and witnessed apneas. The study showed very severe OSA (AHI 137 events/hr), SpO₂ nadir 83%, and SpO₂ < 90% for 69% of total sleep time. Awake TcCO₂ was 52–56 mmHg, remaining >55 mmHg for >10 minutes during sleep, meeting criteria for sleep-related hypoventilation. His serum bicarbonate level was 31 mmol/L, raising concern for obesity-related hypoventilation. CPAP titration normalized his AHI, but the patient remained profoundly PAP-intolerant despite repeated trials and mask desensitization. In April 2023, semaglutide was initiated Over 18 months, the patient lost 70 lbs (250 → 180 lbs) and reported improved dyspnea, reduced sleepiness (Epworth sleepiness scale ESS 14 → 1), and resolution of insomnia (Insomnia severity index ISI 10 → 3). A repeat PSG in October 2024, performed entirely in non-supine position similar to baseline, demonstrated mild OSA (AHI 9.1 events/hr) with similar REM sleep time for comparison. Oxygenation normalized, and follow-up serum bicarbonate level decreased to 27 mmol/L, suggesting reduction of persistent hypercapnia. By late 2025, the patient remained asymptomatic without PAP or oral appliance therapy. Conclusion This case illustrates a 94% reduction in AHI and resolution of obesity-related hypoventilation following semaglutide-associated weight loss in a PAP-intolerant patient with very severe OSA. Consistent sleep positions and REM time between both PSGs, along with improvement in serum bicarbonate level, support a true physiologic reversal rather than positional or technical artifact. GLP-1 RAs may serve as a valuable adjunct or alternative therapy for select patients with severe obesity-related OSA who cannot tolerate device-based treatments. Support (if any) n/a