{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:49:49Z","timestamp":1791931789672,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T00:00:00Z","timestamp":1647561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Pioglitazone is a potent insulin\u2010sensitizing drug with anti\u2010atherosclerotic properties, but adverse effects have limited its use. We assessed the benefits and risks of lower versus higher doses of pioglitazone taken by participants in the Insulin Resistance Intervention in Stroke Trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Efficacy [myocardial infarction (MI) or recurrent stroke] new\u2010onset diabetes) and adverse outcomes (oedema, weight gain, heart failure and bone fracture) were examined for subjects assigned to pioglitazone or placebo within strata defined by mode dose of study drug taken (i.e. the dose taken on most days in the study).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the 1938 patients randomized to pioglitazone, the mode dose was &lt;15\u2009mg\/day in 546 participants, 15\u2009mg\/day in 128, 30\u2009mg\/day in 89, and 45\u2009mg\/day in 1175. There was no significant effect on stroke\/MI or new\u2010onset diabetes with &lt;15\u2009mg\/day. For 15\u2009mg\/30\u2009mg\/day pooled, the adjusted hazard ratios (95% CI) for stroke\/MI were 0.48 (0.30, 0.76;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.002) and 0.74 (0.69, 0.94) for 45\u2009mg\/day. For new\u2010onset diabetes, the adjusted hazard ratios were 0.34 (0.15, 0.81;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.001) and 0.31 (0.59, 0.94;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.001) respectively.\n                    <\/jats:p>\n                    <jats:p>For oedema, weight gain and heart failure, the risk estimates for pioglitazone were lower for subjects taking &lt;45\u2009mg daily. For fractures, the increased risk with pioglitazone was similar across all dose strata.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Lower doses of pioglitazone appear to confer much of the benefit with less adverse effects than the full dose. Further study is needed to confirm these findings so that clinicians may optimize dosing of this secondary prevention strategy in patients with stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14687","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T01:26:01Z","timestamp":1646616361000},"page":"1150-1158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Efficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients with insulin resistance"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7478-1098","authenticated-orcid":false,"given":"J. 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