{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:29:49Z","timestamp":1777984189821,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020430","name":"LG Chem","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020430","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":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate the efficacy and safety of adding a fourth oral antidiabetic drug versus metformin uptitration in patients with type 2 diabetes inadequately controlled with oral triple therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      In this 24\u2010week, randomized, open\u2010label trial, adults with type 2 diabetes having glycated haemoglobin (HbA\n                      <jats:sub>1C<\/jats:sub>\n                      ) 7.0\u20139.0% despite oral triple therapy with metformin plus a thiazolidinedione (TZD), sodium\u2013glucose cotransporter 2 inhibitor (SGLT2i), or dipeptidyl peptidase 4 inhibitor (DPP\u20104i) were randomized to an oral quadruple add\u2010on group or a metformin uptitration group. The quadruple group received the class not previously used (TZD, SGLT2i, or DPP\u20104i), whereas the metformin uptitration group increased the metformin dose by up to 500\u2009mg per day. The primary endpoint was the change in HbA\n                      <jats:sub>1C<\/jats:sub>\n                      at week 24. Secondary endpoints included fasting glucose, metabolic parameters, and safety.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Hundred and ninety\u2010three were evaluable: 48 in the metformin uptitration group and 145 in the quadruple group. Compared to baseline, HbA\n                      <jats:sub>1C<\/jats:sub>\n                      at week 24 decreased by 0.70% (interquartile range [IQR] 0.40%, 1.10%) with quadruple therapy and 0.40% (IQR 0.10%, 0.80%) with metformin uptitration (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). The rate achieving HbA\n                      <jats:sub>1C<\/jats:sub>\n                      \u22647.0% was higher in the quadruple group (69.7% vs. 47.9%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006). Insulin resistance improved only in the quadruple group and was accompanied by reduced albuminuria. Adverse events were mild and comparable between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Oral quadruple therapy achieved greater glycaemic and metabolic improvement without compromising safety, compared with metformin uptitration, supporting its role as an intensification strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70527","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T08:38:14Z","timestamp":1770107894000},"page":"3305-3316","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of adding a fourth oral antidiabetic drug versus metformin dose escalation in patients with type 2 diabetes inadequately controlled on triple oral combination therapy (\n                    <scp>EFFORT<\/scp>\n                    ): A 24\u2010week, randomized, open\u2010label, multicenter trial"],"prefix":"10.1111","volume":"28","author":[{"given":"So Ra","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun Hwa","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Daejeon Eulji Medical Center, Eulji University  Daejeon Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7430-3675","authenticated-orcid":false,"given":"Sin Gon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Korea University College of Medicine  Seoul Republic of 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