Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis on Responder-Based Outcomes and Between-Study Heterogeneity

Background: Hypoglossal nerve stimulation (HNS) is an established surgical therapy for adults with moderate-to-severe obstructive sleep apnea (OSA) who are intolerant to positive airway pressure. Although aggregate response rates of ~70–80% have been reported, substantial variability across clinical settings remains poorly understood. Prior meta-analyses have largely emphasized pooled continuous outcomes, limiting interpretation of responder-based endpoints and drivers of between-study heterogeneity. Methods: A PRISMA-compliant systematic review and meta-analysis was performed. MEDLINE, Embase, and Cochrane CENTRAL were searched from inception through 31 December 2025. Eligible studies enrolled adults with OSA treated with implantable HNS, reported Sher-defined response (≥50% AHI reduction and residual AHI < 20 events/hour), and/or continuous outcomes, and included ≥20 patients. Random-effects models (REML) were applied. Heterogeneity was quantified using I2 and τ2, with prediction intervals. Meta-regression assessed baseline AHI, BMI, and follow-up duration. Subgroup analyses examined device laterality, stimulation modality, sleep assessment method, and follow-up. Results: Thirty-eight studies (39 cohorts; n = 3220) were included. The pooled Sher response rate was 74.0% (95% CI 67.6–79.5%). Heterogeneity was substantial. HNS significantly improved all continuous outcomes (AHI −23.3 events/hour; ESS −4.5 points; ODI −14.5 events/hour). Comparative analyses favored HNS over surgical comparators, inactive stimulation, and delayed treatment. Revision and explantation rates were 5% and 4%, respectively. Meta-regression showed no significant effects of baseline AHI, BMI, or follow-up, explaining negligible variance. Subgroups suggested numerically higher response with breathing-synchronized stimulation, but heterogeneity remained high. Conclusions: HNS achieves Sher response in approximately three-quarters of appropriately selected CPAP-intolerant OSA patients, with durable clinical benefits and a favorable safety profile. Persistent unexplained heterogeneity highlights limitations of conventional predictors and underscores the need for more granular response determinants.