{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:06:04Z","timestamp":1792069564658,"version":"4.4.0"},"reference-count":123,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Background: Obstructive sleep apnea (OSA) is a highly prevalent and heterogeneous disorder associated with substantial cardiometabolic morbidity. Although continuous positive airway pressure (CPAP) remains first-line therapy, long-term effectiveness is frequently limited by suboptimal adherence. Advances in airway devices, surgical techniques, neuromodulation, and pharmacologic therapies have expanded the therapeutic landscape and created opportunities for individualized, mechanism-based treatment. Methods: We conducted a selective, narrative review with structured quantitative synthesis of randomized controlled trials, comparative cohorts, long-term follow-up studies, registries, and mechanistic investigations addressing OSA therapies beyond CPAP. Evidence spanning oral appliances, upper-airway and skeletal surgery, hypoglossal nerve stimulation, neuromuscular electrical stimulation, positional therapy, and pharmacologic interventions targeting metabolic and non-anatomical endotypes was integrated. Outcomes of interest included apnea\u2013hypopnea index (AHI), oxygenation, blood pressure, patient-reported symptoms, durability, safety, and real-world adherence. Results: Mandibular advancement devices (MADs) consistently reduced AHI relative to placebo and produced symptom relief comparable to CPAP in mild-to-moderate OSA, largely due to superior adherence. Palatal surgery yielded meaningful short-term improvement in selected patients but demonstrated limited long-term durability. In contrast, maxillomandibular advancement (MMA) achieved the largest and most durable reductions in OSA severity, with efficacy comparable to CPAP and superior to other surgical modalities in appropriate skeletal phenotypes. Hypoglossal nerve stimulation (HNS) produced substantial, durable improvements in AHI and symptoms with high adherence, supported by randomized trials, long-term follow-up, and real-world registry data; newer bilateral and proximal stimulation systems may further broaden candidacy. Neuromuscular electrical stimulation and positional therapy provided modest, phenotype-dependent benefits, primarily as adjunctive or early-stage interventions. A major advance is the emergence of metabolic and endotype-targeted pharmacotherapy: longitudinal data demonstrate a dose-dependent relationship between weight change and OSA progression or regression, while randomized trials show that GLP-1-based therapies\u2014particularly dual GLP-1\/GIP agonism with tirzepatide\u2014produce large, clinically meaningful reductions in AHI and cardiometabolic risk in obesity-associated OSA. Additional pharmacologic strategies targeting ventilatory loop gain and arousal threshold further support an endotype-driven treatment paradigm. Conclusions: Contemporary OSA management is shifting from a CPAP-centric model toward a precision-guided, multimodal framework that aligns therapy with dominant anatomic and physiological contributors to airway collapse. Integrating metabolic, neuromodulatory, and structural interventions\u2014often in combination\u2014offers the potential for durable disease control and improved patient-centered outcomes. Future priorities include head-to-head and combination trials, long-term cardiovascular outcomes, cost-effectiveness analyses, and pragmatic tools to operationalize personalized OSA therapy in routine clinical practice.<\/jats:p>","DOI":"10.3390\/pathophysiology33010020","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T14:06:56Z","timestamp":1772460416000},"page":"20","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Redefining Obstructive Sleep Apnea: Treatment in the Modern Era"],"prefix":"10.3390","volume":"33","author":[{"given":"Jose","family":"Redondo","sequence":"first","affiliation":[{"name":"Internal Medicine, Jackson Memorial Hospital and University of Miami, 1611 NW 12th Ave, Miami, FL 33136, USA"},{"name":"Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kori B.","family":"Ascher","sequence":"additional","affiliation":[{"name":"Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136, USA"},{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, University of Miami, 1611 NW 12th Ave, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre R.","family":"Abreu","sequence":"additional","affiliation":[{"name":"Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136, USA"},{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, University of Miami, 1611 NW 12th Ave, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1056\/NEJM199304293281704","article-title":"The Occurrence of Sleep-Disordered Breathing among Middle-Aged Adults","volume":"328","author":"Young","year":"1993","journal-title":"N. 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