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Global longitudinal strain (GLS) is an indicator of left ventricular (LV) mechanics and can detect subclinical myocardial dysfunction. We compared the effects of pioglitazone and empagliflozin on GLS in patients with T2DM and NAFLD without established atherosclerotic cardiovascular disease.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This study was a 24-week randomized, single-blind, and parallel-group (1: 1 ratio) clinical trial. Seventy-three participants with T2DM (being treated with metformin) and NAFLD but without established atherosclerotic cardiovascular disease (ASCVD) were randomized to empagliflozin or pioglitazone. Liver steatosis and fibrosis were measured using transient elastography, and GLS was measured by echocardiography. The primary endpoint was the change in GLS from baseline to week 24. Secondary end points include changes in controlled attenuation parameter (CAP) and Liver stiffness measure (LSM).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In this study, GLS improved by 1.56\u2009<jats:underline>\u00b1<\/jats:underline>\u20092.34% (P\u2009&lt;\u20090.01) in the pioglitazone group and 1.06\u2009<jats:underline>\u00b1<\/jats:underline>\u20091.83% (P\u2009&lt;\u20090.01) in the empagliflozin group without a significant difference between the two groups (P\u2009=\u20090.31). At baseline, GLS was inversely associated with the severity of liver fibrosis: r\u2009=\u2009\u2212\u20090.311, P\u2009=\u20090.007. LSM in the pioglitazone and empagliflozin group [(-0.73\u2009<jats:underline>\u00b1<\/jats:underline>\u20091.59) and (-1.11\u2009<jats:underline>\u00b1<\/jats:underline>\u20091.33)] kpa (P\u2009&lt;\u20090.01) decreased significantly. It was without substantial difference between the two groups (P\u2009=\u20090.26). Empagliflozin and pioglitazone both improved controlled attenuation parameter. The improvement was more critical in the empagliflozin group: -48.22\u2009+\u200935.02 dB\/m vs. -25.67\u2009+\u200941.50 dB\/m, P\u2009=\u20090.01.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Subclinical cardiac dysfunction is highly important in patients with T2DM and with NAFLD. Empagliflozin and Pioglitazone improve LV mechanics and fibrosis in patients without established ASCVD. This has a prognostic importance on cardiovascular outcomes in high-risk patients with T2DM. Moreover, empagliflozin ameliorates liver steatosis more effectively them pioglitazone. This study can serve as a start point hypothesis for the future. Further studies are needed to explore the concept in larger populations.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>: This trial was registered in the Iranian Registry of Clinical Trials (IRCT): \u201cA Comparison between the Effect of Empagliflozin and Pioglitazone on Echocardiographic Indices in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease\u201d IRCT20190122042450N5, 29 November 2020. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.irct.ir\/search\/result?query=IRCT20190122042450N5\">https:\/\/www.irct.ir\/search\/result?query=IRCT20190122042450N5<\/jats:ext-link>.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12876-023-02948-4","type":"journal-article","created":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T09:02:20Z","timestamp":1695459740000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Effect of Empagliflozin and Pioglitazone on left ventricular function in patients with type two diabetes and nonalcoholic fatty liver disease without established cardiovascular disease: a randomized single-blind clinical trial"],"prefix":"10.1186","volume":"23","author":[{"given":"Fereshte","family":"Attaran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepideh","family":"Emami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoudreza","family":"Sohrabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojtaba","family":"Malek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Ajdarkosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoodreza","family":"Khoonsari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faramarz","family":"Ismail-Beigi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad E.","family":"Khamseh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,23]]},"reference":[{"issue":"5","key":"2948_CR1","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1007\/s10620-016-4085-6","volume":"61","author":"HL Reeves","year":"2016","unstructured":"Reeves HL, Zaki MY, Day CP. 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