CPAP Most Effective for Apnea-Hypopnea Index, GLP-1 RAs Improve Weight in OSA

This network meta-analysis evaluated the comparative efficacy of continuous positive airway pressure (CPAP), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), their combination, and no active intervention in adults with obstructive sleep apnea (OSA). The analysis included 3964 participants across multiple trials. The primary outcome was the apnea-hypopnea index (AHI), and secondary outcomes included Epworth Sleepiness Scale (ESS), body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), fasting glucose, and glycated haemoglobin (HbA1c).

For the primary outcome, CPAP produced the largest reduction in AHI versus no active intervention, with a mean difference (MD) of -22.17 events/h (95% CI -38.01 to -6.33). This effect was statistically significant and clinically meaningful, as a reduction of this magnitude typically moves patients from moderate-to-severe OSA to mild or no disease. CPAP also improved ESS scores (MD -2.75, 95% CI -3.71 to -1.79), indicating reduced daytime sleepiness.

Regarding metabolic outcomes, liraglutide significantly reduced BMI (MD -1.60 kg/m², 95% CI -2.04 to -1.16) and HbA1c (MD -0.19%, 95% CI -0.25 to -0.13) compared to no active intervention. The combination of liraglutide plus CPAP achieved the greatest BMI reduction (MD -2.00 kg/m², 95% CI -3.49 to -0.51). However, no intervention significantly changed SBP, DBP, or fasting glucose.

Safety and tolerability data were not reported in this meta-analysis, which is a notable limitation. Adverse events, serious adverse events, and discontinuations were not available, so the risk-benefit profile of these interventions cannot be fully assessed from this analysis alone.

Compared to prior landmark studies, these results confirm CPAP as the gold standard for improving respiratory parameters and sleepiness in OSA. The addition of GLP-1 RAs, particularly liraglutide, offers metabolic benefits that CPAP alone does not provide. This aligns with the growing recognition of OSA as a metabolic disorder, where weight reduction can improve disease severity and cardiovascular risk.

Key methodological limitations include the moderate certainty of evidence for CPAP effects on respiratory and sleepiness outcomes and for GLP-1 RAs on BMI and HbA1c. Certainty was low for blood pressure and fasting glucose outcomes. The network meta-analysis design relies on indirect comparisons, which may introduce bias if trials differ in patient characteristics or protocols. Additionally, the absence of safety data limits clinical applicability.

Clinically, these findings support an integrated airway-metabolic approach to OSA management. CPAP remains first-line for respiratory control, while GLP-1 RAs may be considered adjunctive therapy for patients with obesity or impaired glucose metabolism. However, the lack of safety data and low certainty for some outcomes warrant cautious interpretation. Future research should directly compare GLP-1 RAs with CPAP and their combination, and include long-term safety and cardiovascular outcomes.