{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T06:34:33Z","timestamp":1787380473268,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,6,3]],"date-time":"2013-06-03T00:00:00Z","timestamp":1370217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:p>\n                    The main pathogenesis of type 2 diabetes mellitus (\n                    <jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content>\n                    ) includes insulin resistance and pancreatic islet dysfunction. Metformin, which attenuates insulin resistance, has been recommended as the first\u2010line antidiabetic medication.\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/en.wikipedia.org\/wiki\/Dipeptidyl_peptidase-4\">Dipeptidyl peptidase\u20104<\/jats:ext-link>\n                    (\n                    <jats:styled-content style=\"fixed-case\">DPP<\/jats:styled-content>\n                    \u20104) inhibitors are novel oral hypoglycaemic agents that protect glucagon\u2010like peptide\u20101 (\n                    <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\n                    \u20101) from degradation, maintain the bioactivity of endogenous\n                    <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\n                    \u20101, and thus improve islet dysfunction. Results from clinical trials have shown that the combination therapy of\n                    <jats:styled-content style=\"fixed-case\">DPP<\/jats:styled-content>\n                    \u20104 inhibitors and metformin [as an add\u2010on, an initial combination or a fixed\u2010dose combination (FDC)] provides excellent efficacy and safety in patients with\n                    <jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content>\n                    . Moreover, recent studies have suggested that metformin enhances the biological effect of\n                    <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\n                    \u20101 by increasing\n                    <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\n                    \u20101 secretion, suppressing activity of\n                    <jats:styled-content style=\"fixed-case\">DPP<\/jats:styled-content>\n                    \u20104 and upregulating the expression of\n                    <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\n                    \u20101 receptor in pancreatic \u03b2\u2010cells. Conversely,\n                    <jats:styled-content style=\"fixed-case\">DPP<\/jats:styled-content>\n                    \u20104 inhibitors have a favourable effect on insulin sensitivity in patients with\n                    <jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content>\n                    . Therefore, the combination of\n                    <jats:styled-content style=\"fixed-case\">DPP<\/jats:styled-content>\n                    \u20104 inhibitors and metformin provides an additive or even synergistic effect on metabolic control in patients with\n                    <jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content>\n                    . This article provides an overview of clinical evidence and discusses the rationale for the combination therapy of\n                    <jats:styled-content style=\"fixed-case\">DPP<\/jats:styled-content>\n                    \u20104 inhibitors and metformin.\n                  <\/jats:p>","DOI":"10.1111\/dom.12128","type":"journal-article","created":{"date-parts":[[2013,5,13]],"date-time":"2013-05-13T12:54:43Z","timestamp":1368449683000},"page":"111-117","source":"Crossref","is-referenced-by-count":43,"title":["Combination therapy of dipeptidyl peptidase\u20104 inhibitors and metformin in type 2 diabetes: rationale and evidence"],"prefix":"10.1111","volume":"16","author":[{"given":"Y.","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Peking University Third Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of 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