Alternatives to positive airway pressure devices for obstructive sleep apnea: a phenotype-guided review

INTRODUCTION: Continuous positive airway pressure (PAP) is the reference treatment for obstructive sleep apnea (OSA); however, limited adherence leaves many patients inadequately treated, creating a pressing need for effective alternatives matched to individual disease mechanisms. AREAS COVERED: This review examines the principal alternatives to PAP - custom oral appliances, upper airway and adherence-directed surgery, hypoglossal nerve stimulation, positional therapy, myofunctional and respiratory muscle training, daytime neuromuscular stimulation, neuromuscular pharmacotherapy, and weight-directed incretin therapy in adults. For each, we summarize indications, evidence, and limitations, and integrate drug-induced sleep endoscopy, bedside functional testing, and physiological endotyping into candidate selection. PubMed/MEDLINE and the Cochrane Library were searched from January 2005 through July 2026 using combinations of 'obstructive sleep apnea,' 'CPAP alternative,' 'phenotype,' 'endotype,' 'drug-induced sleep endoscopy,' and each modality's name; pivotal randomized trials, current clinical practice guidelines, and mechanistic studies from high-impact journals were prioritized, supplemented by hand-searching reference lists. EXPERT OPINION: OSA care is shifting from a one-size-fits-all model toward phenotype-guided precision management. The first approved drug therapy, the maturation and broadening of hypoglossal nerve stimulation, and endotype-targeted pharmacotherapy will make mechanism-based selection and rational combination therapy the central task for clinicians treating patients unable to use PAP.