{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T23:24:43Z","timestamp":1778541883521,"version":"3.51.4"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":54,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Centro de Farmacovigilancia, Investigaci\u00f3n y Detecci\u00f3n Temprana de Alteraciones Cl\u00ednicas"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>High-dose pregabalin is effective for painful diabetic peripheral neuropathy, but dose-dependent adverse effects limit its use. Thioctic acid (alpha-lipoic acid), a mitochondrial antioxidant with neuromodulatory properties, may improve tolerability without reducing efficacy when combined with lower doses of pregabalin. We conducted a multicenter, double-blind, parallel-group, non-inferiority trial at nine centers in Mexico between November 2017 and March 2020. Adults with painful diabetic peripheral neuropathy underwent pregabalin titration. Non-responders, defined as patients with &amp;lt;50% pain reduction, were randomized in a 1:1 ratio to receive pregabalin 150\u2005mg twice daily or a fixed-dose combination of pregabalin 80\u2005mg plus thioctic acid 400\u2005mg twice daily for 12 weeks. The primary endpoint was mean pain intensity at week 12, measured using a 10-point visual analogue scale, analysed in the per-protocol population with a predefined non-inferiority margin of 0.735. Of 645 participants screened, 439 were randomized (220 to pregabalin and 219 to the combination). In the per-protocol population (n = 297), the adjusted mean between-group difference in pain scores was 0.04 (upper 99.17% confidence interval: 0.62), confirming the non-inferiority of the combination regimen compared with standard-dose pregabalin. Pain trajectories over time, responder rates defined by at least 30% and at least 50% pain reduction, and patient-reported outcomes, including the Short-Form McGill Pain Questionnaire, the 36-Item Short Form Health Survey, and the Leeds Assessment of Neuropathic Symptoms and Signs scale, showed similar point estimates. However, non-inferiority was not formally demonstrated for these secondary measures. Exploratory post-hoc subgroup analyses suggested numerically greater effects among patients with a body mass index above 25 or disease duration of more than 2 years. In the intention-to-treat safety population, the combination group reported significantly fewer dose-limiting adverse events, particularly dizziness (34% versus 52%) and dry mouth (10% versus 20%), without an increase in serious adverse events. A fixed-dose combination of low-dose pregabalin and thioctic acid is non-inferior to high-dose pregabalin for analgesic efficacy and demonstrates an improved safety profile. These findings support this combination as a safe and better-tolerated treatment alternative for painful diabetic peripheral neuropathy.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag058","type":"journal-article","created":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T12:31:11Z","timestamp":1771763471000},"source":"Crossref","is-referenced-by-count":1,"title":["Combination therapy with pregabalin and thioctic acid offers safer pain control in diabetic neuropathy: a multicenter, double-blind, non-inferiority trial"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2642-9831","authenticated-orcid":false,"given":"Edith","family":"Z\u00e1rate","sequence":"first","affiliation":[{"name":"Psicofarma S.A. de C.V. , Mexico City 04380 ,","place":["M\u00e9xico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidia Viridiana","family":"Vel\u00e1squez-Reyes","sequence":"additional","affiliation":[{"name":"Psicofarma S.A. de C.V. , Mexico City 04380 ,","place":["M\u00e9xico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Carlos Espindola-Reyes","sequence":"additional","affiliation":[{"name":"Psicofarma S.A. de C.V. , Mexico City 04380 ,","place":["M\u00e9xico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Bravo-Lamicq","sequence":"additional","affiliation":[{"name":"Psicofarma S.A. de C.V. , Mexico City 04380 ,","place":["M\u00e9xico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8759-7116","authenticated-orcid":false,"given":"Diego Antonio","family":"Ocampo-Guti\u00e9rrez de Velasco","sequence":"additional","affiliation":[{"name":"Psicofarma S.A. de C.V. , Mexico City 04380 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