{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:56:50Z","timestamp":1786121810807,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100019265","name":"Yuhan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To assess the efficacy and safety of alpha\u2010lipoic acid (ALA) and pregabalin, both as mono and combination therapy, for treating painful diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus, with the hypothesis that pregabalin monotherapy is non\u2010inferior to combination therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>A phase 4 randomized, active\u2010controlled, open\u2010label, multicentre trial was conducted over 12\u2009weeks to investigate changes in visual analogue scale (VAS) pain scores from baseline as a primary efficacy endpoint. A total of 151 eligible subjects were randomly assigned to ALA (480\u2009mg\/day), pregabalin (150\u2009mg\/day), and combination groups in a 1:1:1 ratio.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The pregabalin monotherapy group showed a VAS change of \u221219.73\u2009\u00b1\u200918.94\u2009mm, while the combination group showed \u221223.28\u2009\u00b1\u200918.15\u2009mm at Week 12. The least square mean (LSM) difference between the two groups was 3.46\u2009mm (95% CI: [\u22124.94, 11.87]), demonstrating that pregabalin monotherapy is non\u2010inferior to combination therapy. Safety analysis revealed no significant differences across treatment groups. Cluster analysis revealed statistically significant differences in VAS scores between the pregabalin monotherapy and combination therapy groups at 12\u2009weeks in cluster 1, characterized by a relatively shorter duration of DPN, and the LSM difference between both groups was 14.79\u2009mm [4.59, 24.99] (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0055).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The pregabalin monotherapy demonstrated non\u2010inferiority compared to the combination therapy in alleviating DPN pain. Cluster analysis supported the identification of patient groups where combination therapy could be more effective, but future comprehensive studies are required for further verification.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      , NCT04846673\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70795","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:11:38Z","timestamp":1777518698000},"page":"6172-6183","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Pregabalin and Alpha\u2010Lipoic Acid Combination in Patients With Painful Diabetic Peripheral Neuropathy: A Randomized, Open\u2010Label, Non\u2010Inferiority, Phase\n                    <scp>IV<\/scp>\n                    Clinical Trial and Subgroup Analysis (\n                    <scp>OPTIMUM Study<\/scp>\n                    )"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5078-6123","authenticated-orcid":false,"given":"Tae Jung","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Seoul National University College of Medicine and Seoul National University Bundang Hospital  Seongnam Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine Pusan National University Hospital  Busan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Hwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine The Catholic University of Korea, Seoul St. Mary's Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4026-4572","authenticated-orcid":false,"given":"Hyuk\u2010Sang","family":"Kwon","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine The Catholic University of Korea, Yeouido St. Mary's Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Sook","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine The Catholic University of Korea, Incheon St. Mary's Hospital  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6108-7758","authenticated-orcid":false,"given":"Eun\u2010Jung","family":"Rhee","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Jin","family":"Yoo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine Korea University Guro Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han Na","family":"Jang","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine  Seoul Republic of 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