Comparative effectiveness and safety of novel antidiabetic agents in the management of obstructive sleep apnea: a systematic review, meta-analysis, and network meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is a prevalent but frequently underdiagnosed type of sleep-disordered breathing. Excessive obesity is a primary reversible risk factor for OSA. A range of novel antidiabetic agents has recently demonstrated promising potential for improving OSA severity through weight loss and metabolic regulation. OBJECTIVE: This study aimed to examine the effectiveness and safety of novel antidiabetic agents for people with OSA. METHODS: We searched PubMed, Web of Science, Cochrane Library, and Embase database from inception to May 18, 2025. Pairwise meta-analysis and Bayesian network meta-analysis (NMA) were conducted to compare relative efficacy. RESULTS: A total of 8 RCTs and 2 non-RCTs involving 1280 OSA participants were enrolled. Compared with the control group, SGLT-2i (MD = -7.73 events/h, 95 % CI [-9.83, -5.64]), GLP-1 RAs (MD = -5.19 events/h, 95 % CI [-6.87, -3.51]), and tirzepatide (-21.89 events/h, 95 % CI [-26.01, -17.77]) could significantly decrease AHI. The NMA results suggested that tirzepatide ranking highest of producing the greatest AHI reduction (MD = -21.85 events/h, 95 % CI [-27.52, -16.34]), along with the most substantial decreases in body weight (MD = -19.41 kg, 95 % CI [-21.00, -17.82]) and blood pressure (MD = -5.86 mmHg, 95 % CI [-7.97, -3.74]; MD = -1.96 mmHg, 95 % CI [-3.45, -0.46]). CONCLUSION: Based on indirect evidence, tirzepatide was associated with the largest estimated magnitude of AHI reduction, presumably mediated by its weight-loss effects. For obesity-related OSA patients intolerant to continuous positive airway pressure therapy, tirzepatide may represent a potential adjunctive or alternative pharmacological option. High-quality studies are still needed to validate these findings further. PROSPERO REGISTRATION NUMBER: CRD420251165267.