{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:21:50Z","timestamp":1787923310069,"version":"build-2784847793"},"reference-count":75,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013129","name":"Ministry of SMEs and Startups","doi-asserted-by":"publisher","award":["RS-2023-00321754"],"award-info":[{"award-number":["RS-2023-00321754"]}],"id":[{"id":"10.13039\/501100013129","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2023-00321754"],"award-info":[{"award-number":["RS-2023-00321754"]}],"id":[{"id":"https:\/\/ror.org\/022c4zk48","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Soonchunhyang University Research Fund"},{"id":[{"id":"https:\/\/ror.org\/03qjsrb10","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Obstructive sleep apnea (OSA) remains under-treated because continuous positive airway pressure, though efficacious, is frequently limited by poor tolerance and adherence. Long considered a purely anatomical disease refractory to drugs, OSA is now understood as the shared endpoint of four measurable endotypes\u2014a collapsible upper airway, poor pharyngeal dilator-muscle responsiveness, high loop gain, and a low arousal threshold\u2014each a distinct pharmacological target. This review synthesizes the mechanistic rationale and clinical evidence for targeting them. Methods: In this narrative review, we searched PubMed\/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (January 2000 to February 2026) for randomized trials, meta-analyses, and mechanistic endotyping studies, appraising the evidence narratively. Results: Tirzepatide became the first drug approved for OSA, acting through weight loss to reduce obesity-related mechanical loading, and the noradrenergic\u2013antimuscarinic combination AD109 met its primary endpoint in a pivotal phase 3 trial by targeting dilator-muscle activity independently of weight. Both, however, used AHI-based endpoints in clinically defined rather than endotype-selected populations; AD109\u2019s placebo-corrected effect was modest (\u22124.0 events\/h), and 21.2% versus 3.1% of participants discontinued for adverse events. They are therefore best described as mechanism-informed rather than endotype-validated. Carbonic anhydrase inhibition with acetazolamide or sultiame and selected sedating agents address ventilatory instability and a low arousal threshold, while solriamfetol and pitolisant relieve residual sleepiness. Conclusions: Mechanism-informed pharmacotherapy for OSA is now clinically credible, but scalable bedside endotyping, attention to tolerability, and trait-stratified trials are needed before treatment can be called endotype-guided.<\/jats:p>","DOI":"10.3390\/ph19091361","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:27:46Z","timestamp":1787920066000},"page":"1361","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Precision Pharmacotherapy for Obstructive Sleep Apnea: Matching Targeted Drugs to Patient Endophenotypes"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5905-057X","authenticated-orcid":false,"given":"Jayoung","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan 31151, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5194-930X","authenticated-orcid":false,"given":"Ji Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/S0140-6736(13)60734-5","article-title":"Adult obstructive sleep apnoea","volume":"383","author":"Jordan","year":"2014","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1056\/NEJMoa043104","article-title":"Obstructive sleep apnea as a risk factor for stroke and death","volume":"353","author":"Yaggi","year":"2005","journal-title":"N. 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