Frontiers in Neurology · Oct 30, 2026
Comparative Efficacy of Weight-Loss and Diuretic-Based Pharmacotherapies for Obstructive Sleep Apnea: A Systematic Review and Network Meta-Analysis
By Yong Liu, Yuehua Xiang
Purpose: This study aims to compare the relative efficacy of weight-loss-centric pharmacotherapies (GLP-1/GIP agonists) versus fluid-targeting therapies (MRAs, SGLT-2 inhibitors, and diuretics) in reducing the severity of obstructive sleep apnea (OSA) and improving cardiovascular markers. Methods: We conducted a systematic review and frequentist random-effects network meta-analysis of randomized controlled trials (RCTs) from PubMed, Embase, and Cochrane Library through June 2024. The primary outcome was the mean difference (MD) in the Apnea-Hypopnea Index (AHI). Secondary outcomes included changes in systolic blood pressure (SBP) and body mass index (BMI). Results: Fifteen randomized trials involving 1,371 participants were included. Compared with placebo, the mineralocorticoid receptor antagonist (MRA) spironolactone (MD −22.68 events/h; 95% CI, −25.42 to −19.93) and the dual GLP-1/GIP agonist tirzepatide (MD −21.96 events/h; 95% CI, −26.16 to −17.76) demonstrated the highest efficacy in AHI reduction. Tirzepatide achieved AHI reduction through significant weight loss, whereas MRAs and SGLT-2 inhibitors reduced OSA severity without significant BMI changes. Subgroup analysis confirmed that incretins were most effective in obesity-dominant OSA (P=0.008), while MRAs were highly effective in fluid-retention phenotypes. Conclusions: Both metabolic weight-loss and circulatory fluid-clearance pathways are potent targets for OSA pharmacotherapy. Tirzepatide and spironolactone represent the most effective agents for their respective phenotypes. These findings support a precision medicine approach where pharmacotherapy is tailored to the patient's clinical phenotype (obesity vs. fluid retention/hypertension).