{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:12:14Z","timestamp":1790957534069,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R01DK103841\u201001A1"],"award-info":[{"award-number":["1R01DK103841\u201001A1"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK107680"],"award-info":[{"award-number":["R01DK107680"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["R01DK24092\u201034"],"award-info":[{"award-number":["R01DK24092\u201034"]}],"id":[{"id":"10.13039\/100000041","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":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To compare the efficacy of triple therapy (metformin\/exenatide\/pioglitazone) versus stepwise conventional therapy (metformin\u2009\u2192\u2009glipizide\u2009\u2192\u2009glargine insulin) on liver fat content and hepatic fibrosis in newly diagnosed, drug\u2010na\u00efve patients with type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixty\u2010eight patients completed the 6\u2010year follow\u2010up and had an end\u2010of\u2010study (EOS) FibroScan to provide measures of steatosis (controlled attenuation parameter [CAP] in dB\/m) and fibrosis (liver stiffness measurement [LSM] in kPa); 59 had magnetic resonance imaging\u2010proton density fat fraction (MRI\u2010PDFF) to measure liver fat.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At EOS, HbA1c was 6.8% and 6.0% in triple and conventional therapy groups, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.0006). Twenty\u2010seven of 39 subjects (69%) receiving conventional therapy had grade 2\/3 steatosis (CAP, FibroScan) versus nine of 29 (31%) in triple therapy (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.0003). Ten of 39 (26%) subjects receiving conventional therapy had stage 3\/4 fibrosis (LSM) versus two of 29 (7%) in triple therapy (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.04). Conventional therapy subjects had more liver fat (MRI\u2010PDFF) than triple therapy (12.9% vs. 8.8%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.03). The severity of steatosis (CAP) (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a00.42,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.001) and fibrosis (LSM) (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a0\u22120.48,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.001) correlated inversely with the Matsuda Index of insulin sensitivity, but not with percentage body fat. Aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), non\u2010alcoholic fatty liver disease fibrosis score (NFS), plasma AST, and alanine aminotransferase (ALT) all decreased significantly with triple therapy, but only the decrease in plasma AST and ALT correlated with the severity of steatosis and fibrosis at EOS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>At EOS, subjects with type 2 diabetes treated with triple therapy had less hepatic steatosis and fibrosis versus conventional therapy; the severity of hepatic steatosis and fibrosis were both strongly and inversely correlated with insulin resistance; and changes in liver fibrosis scores (APRI, NFS, Fibrosis\u20104, and AST\/ALT ratio) have limited value in predicting response to therapy.<\/jats:p>\n                  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