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Pioglitazone, a peroxisome proliferator\u2013activated receptor-\u03b3 agonist with anti-inflammatory and anti-apoptotic properties, has been proposed as a potential adjunctive therapy. In this prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted across five countries, 128 adults with severe to profound unilateral iSSNHL or AT were treated within 96\u00a0h of symptom onset. Patients received standard corticosteroid therapy combined with intratympanic and\/or oral pioglitazone or placebo. Hearing outcomes were assessed using changes in pure-tone audiometry at the most affected frequencies over 12\u00a0weeks. All treatment groups showed significant hearing improvement over time; however, no additional benefit of pioglitazone was observed compared with placebo. Overall hearing thresholds improved substantially, while variations in corticosteroid dose and treatment duration did not influence recovery. These findings indicate that pioglitazone does not enhance hearing recovery when added to corticosteroid therapy, and that higher or prolonged corticosteroid dosing offers no measurable advantage. Further randomized controlled studies are warranted to better define effective treatment strategies for these conditions.<\/jats:p>","DOI":"10.1038\/s41598-026-58366-5","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:36:27Z","timestamp":1782286587000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pioglitazone does not improve standard steroid therapy for severe to profound sudden sensorineural hearing loss"],"prefix":"10.1038","volume":"16","author":[{"given":"Nicole","family":"Peter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"B\u00f6rlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Sommerhalder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Neff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Bausch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Kleinjung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"issue":"8","key":"58366_CR1","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1056\/NEJMcp0802129","volume":"359","author":"SD Rauch","year":"2008","unstructured":"Rauch, S. 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