{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:06:22Z","timestamp":1789535182936,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01 CX001837"],"award-info":[{"award-number":["I01 CX001837"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>Current medications for alcohol use disorders (AUD) are under\u2010used and of moderate benefit; new or improved treatments are much needed. Preclinical and small clinical studies indicate that pioglitazone, a thiazolidinedione agonist of the peroxisome proliferator\u2010activated receptor gamma, may reduce alcohol use. The primary purpose of this study was to evaluate, in a randomized trial, the effect of pioglitazone on alcohol use and craving in adults with AUD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A double\u2010blind, placebo\u2010controlled randomized trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Enrollment occurred in the United States at two Veterans Affairs Health Care Centers (VAHCS) from July 2019 to March 2024.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>One hundred eighty\u2010five Veteran men and women older than 18\u2009years with at least a moderate AUD and current alcohol use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention and comparator<\/jats:title>\n                    <jats:p>\n                      Oral pioglitazone was given at dosages of 0 (placebo) (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200992), or 45\u2009mg (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200993) over 14\u2009weeks. All participants received Brief Behavioral Compliance Enhancement Treatment at each visit.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>The primary outcome measure was the number of heavy drinking days during week 14 as measured by the Timeline Follow Back (TLFB). Secondary measurements included the number of standard drinks consumed per week, the rate of no heavy drinking days over the last 8\u00a0weeks of the study, alcohol craving, anxiety, depression and post\u2010traumatic stress disorder symptoms. Exploratory outcome included change in alcohol use based on inflammation (C\u2010reactive protein) at baseline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      There was no difference between groups on the primary outcome (pioglitazone mean\u2009=\u20092.43, placebo mean\u2009=\u20092.01, difference\u2009=\u20090.43, 95% confidence interval\u2009=\u2009\u22120.25 to 1.10,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.22). No differences were found between groups in secondary alcohol use measures or a measure of craving. Participants with elevated inflammation at baseline treated with pioglitazone had a greater decrease in heavy drinking days over time compared with placebo (z\u2009=\u20092.21,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.03). Pioglitazone was safe and well tolerated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pioglitazone administered to people with alcohol use disorder at a dose of 45\u2009mg per day appears to be safe although there is no evidence that it is efficacious in reducing alcohol use, alcohol craving or any psychiatric measures.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/add.70508","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T03:15:44Z","timestamp":1781147744000},"page":"2661-2670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pioglitazone for the treatment of alcohol use disorder: A randomized controlled trial"],"prefix":"10.1111","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4949-6444","authenticated-orcid":false,"given":"Eric","family":"Dieperink","sequence":"first","affiliation":[{"name":"Minneapolis Veterans Affairs Healthcare Systems  Minneapolis MN USA"},{"name":"University of Minnesota\u2010Medical School Department of Psychiatry  Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Anderson","sequence":"additional","affiliation":[{"name":"Long Beach Veterans Affairs Healthcare Systems  Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Dockter","sequence":"additional","affiliation":[{"name":"Minneapolis Veterans Affairs Healthcare Systems  Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith","family":"Evenson","sequence":"additional","affiliation":[{"name":"Minneapolis Veterans Affairs Healthcare Systems  Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Thuras","sequence":"additional","affiliation":[{"name":"Minneapolis Veterans Affairs Healthcare Systems  Minneapolis MN USA"},{"name":"University of Minnesota\u2010Medical School Department of Psychiatry  Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hauser","sequence":"additional","affiliation":[{"name":"Long Beach Veterans Affairs Healthcare Systems  Minneapolis MN USA"},{"name":"Department of Psychiatry and Neuroscience University of California\u2010Riverside  Riverside CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadr.2024.100310"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00122-1"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.7326\/AITC202210180"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.61.8.807"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/00048674231201541"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2007.08.005"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12010"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1176\/ps.2010.61.4.392"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ps.201000553"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2012.04054.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2008.07.018"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450111314070006"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3159"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12610"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.09.012"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2003.08.064"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0899"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.12.010"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.13868"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajad.13214"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-020-05540-w"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0376-8716(96)01263-X"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.158.16.1789"},{"key":"e_1_2_10_25_1","volume-title":"Structured Clinical Interview for DSM\u20105\u2014Research Version (SCID\u20105 for DSM\u20105, Research Version; 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