Efficacy of SGLT2 inhibitors, GLP-1 receptor agonists, and aerobic exercise for moderate-to-severe obstructive sleep apnea in overweight or obese patients: a network meta-analysis

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Abstract

[OBJECTIVE] Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder strongly linked to obesity and substantially increases the risk of cardiovascular and metabolic diseases. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and aerobic exercise have shown potential in improving OSA through distinct metabolic and physiological mechanisms. However, direct comparative evidence of their efficacy remains limited. This network meta-analysis aimed to compare the effects of SGLT2 inhibitors, GLP-1 receptor agonists, and aerobic exercise on OSA severity in overweight or obese patients. [METHODS] We searched four electronic databases, PubMed, EMBASE, the Cochrane Library, and Web of Science, for articles published before October 31, 2025, without language restrictions. The analysis primarily included randomized controlled trials (RCTs); a limited number of case-control studies were also incorporated due to the scarcity of direct comparative evidence. Primary efficacy outcomes were mean changes in the apnea-hypopnea index (AHI), body mass index (BMI), mean peripheral oxygen saturation (SpO2), and Epworth Sleepiness Scale (ESS) score. The certainty (confidence) of the evidence for every network estimate was appraised with the Confidence in Network Meta-Analysis (CINeMA) framework, which operationalizes the GRADE approach for network meta-analysis. [RESULTS] A total of 15 studies (13 RCTs and 2 case-control studies) involving 1,877 participants were included in the analysis. GLP-1 receptor agonists demonstrated the greatest reduction in AHI compared with placebo (mean difference [MD] = -15.28 events/h; 95% CI, -22.22 to -8.35). They also showed significant benefit versus placebo in lowering BMI (MD = -1.78 kg/m2; 95% CI, -2.15 to -1.41) and improving mean SpO2 (MD = 0.40%; 95% CI, 0.25 to 0.55). Although GLP-1 receptor agonists yielded a statistically significant improvement in ESS score versus placebo (MD = -0.20; 95% CI, -0.26 to -0.14), this effect was an order of magnitude below the 2-point minimal clinically important difference (MCID) for the ESS and is therefore not clinically meaningful. Aerobic exercise ranked highest in surface under the cumulative ranking curve (SUCRA) analysis for this outcome. No network estimate was rated as high certainty. Confidence was moderate for the effect of GLP-1 receptor agonists on BMI, low for their effects on AHI, mean SpO2, and ESS score versus placebo, and very low for all remaining comparisons, mainly because of within-study bias, imprecision, and suspected reporting bias. [CONCLUSION] Compared with placebo, GLP-1 receptor agonists reduced AHI and BMI and improved mean SpO2, and ranked highest for these outcomes in the SUCRA analysis. Comparisons between the active interventions, however, were largely non-significant and rested on indirect evidence, and the certainty of the evidence was moderate at best, being low or very low for most comparisons. This treatment hierarchy should therefore be regarded as hypothesis-generating rather than as a basis for firm clinical recommendations. Within these limits, these findings suggest that GLP-1 receptor agonists may offer a promising therapeutic approach for managing OSA in overweight or obese patients with metabolic comorbidities, though this remains to be confirmed in larger, high-quality, head-to-head trials.

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