{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:16:04Z","timestamp":1792808164521,"version":"4.5.0"},"reference-count":13,"publisher":"Korean Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Jeil Pharmaceutical Co. Ltd."}],"content-domain":{"domain":["e-dmj.org"],"crossmark-restriction":true},"short-container-title":["Diabetes Metab J"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:p>Background: This study investigated the efficacy and safety of pioglitazone 30 mg\/day add-on to inadequately controlled type 2 diabetes mellitus (T2DM) patients with treatment of dapagliflozin and metformin.Methods: In this multicenter (34 sites), double-blind, randomized, phase 3 study, patients with T2DM with an inadequately controlled glycosylated hemoglobin (HbA1c) over 7.0% to treatment with dapagliflozin (10 mg\/day) and metformin (\u22651,000 mg\/day) were randomized to receive additional pioglitazone 30 mg\/day (n=124) or placebo (n=122) for 24 weeks. The primary outcome was the mean change of HbA1c from baseline to 24 weeks treatment. The efficacy and safety were evaluated with open label extension period, switching placebo to pioglitazone 30 mg\/day at 48 weeks (ClinicalTrials.gov identifier: NCT05296044).Results: The HbA1c after 24 weeks treatment reduced from 7.8%\u00b10.8% to 7.0%\u00b10.6% (&lt;i&gt;P&lt;\/i&gt;&lt;0.0001). The proportions of patients who achieved HbA1c less than 7.0% at 24 weeks were significantly higher in pioglitazone add-on group (51.61% in pioglitazone vs. 22.95% in placebo, &lt;i&gt;P&lt;\/i&gt;&lt;0.0001), or less than 6.5% at 24 weeks (21.77% in pioglitazone vs. 2.46% in placebo, &lt;i&gt;P&lt;\/i&gt;&lt;0.0001). Body weight gain was 2.0 kg at 24 weeks with pioglitazone 30 mg\/day and \u20130.6 kg at 24 weeks with placebo.Conclusion: Addition of pioglitazone 30 mg\/day to T2DM patients who did not reach the target HbA1c (\u22647%) with treatment of dapagliflozin 10 mg\/day and metformin over 1,000 mg\/day showed effective glucose lowering efficacy without significant hypoglycemia and good tolerability with low prevalence of edema in spite of modest weight gain.<\/jats:p>","DOI":"10.4093\/dmj.2024.0696","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T08:08:16Z","timestamp":1761638896000},"page":"320-330","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Efficacy and Safety of High-Dose Pioglitazone as Add-on Therapy in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Dapagliflozin and Metformin: Double-Blind, Randomized, Placebo-Controlled Trial"],"prefix":"10.4093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8693-1038","authenticated-orcid":true,"given":"Jun Hwa","family":"Hong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Ah","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You-Cheol","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Gyoung","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang Beom","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Chan","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Chul","family":"Won","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hun-Sung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eui-Hyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwanpyo","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang Hyun","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3597-342X","authenticated-orcid":true,"given":"Kyong Soo","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2567","reference":[{"key":"ref1","first-page":"S181","volume-title":"9.Pharmacologic approaches to glycemic treatment: standards of care in diabetes-2025","year":"2025"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2019.0208"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-024-00836-y"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-019-1270-y"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.14136.1"},{"key":"ref6","first-page":"2606","volume-title":"Effect of combination pioglitazone with sodium-glucose cotransporter-2 inhibitors or glucagon-like peptide-1 receptor agonists on outcomes in type 2 diabetes: a systematic review, meta-analysis, and real-world study from an international federated database","author":"Anson","year":"2024"},{"key":"ref7","first-page":"2188","volume-title":"A multicentre, double-blind, placebo-controlled, randomized, parallel comparison, phase 3 trial to evaluate the efficacy and safety of pioglitazone add-on therapy in type 2 diabetic patients treated with metformin and dapagliflozin","author":"Lim","year":"2024"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2023.0314"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2024.06.023"},{"key":"ref10","first-page":"1279","volume-title":"Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macro-Vascular Events): a randomized controlled trial","author":"Dormandy","year":"2005"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2016.05.060"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa060326"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41854-2"}],"container-title":["Diabetes &amp; Metabolism Journal"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/e-dmj.org\/upload\/pdf\/dmj-2024-0696.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-dmj.org\/journal\/view.php?doi=10.4093\/dmj.2024.0696","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-dmj.org\/upload\/pdf\/dmj-2024-0696.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:39:58Z","timestamp":1773279598000},"score":1,"resource":{"primary":{"URL":"http:\/\/e-dmj.org\/journal\/view.php?doi=10.4093\/dmj.2024.0696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,1]]},"references-count":13,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,3]]}},"URL":"https:\/\/doi.org\/10.4093\/dmj.2024.0696","relation":{},"ISSN":["2233-6079","2233-6087"],"issn-type":[{"value":"2233-6079","type":"print"},{"value":"2233-6087","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,1]]},"assertion":[{"value":"2024-11-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-28","order":2,"name":"published","label":"Published online","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-01","order":3,"name":"published","label":"Print publication","group":{"name":"publication_history","label":"Publication History"}}]}}