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We aimed to examine the decisions by 3 regulatory authorities in response to identical CVOT data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We surveyed <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link> to identify CVOTs and examined the revision histories of drug labels in databases from the FDA, the European Medicines Agency, and the Pharmaceuticals and Medical Devices Agency in Japan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We selected 14 drugs and corresponding CVOTs, 12 of which were conducted as postmarketing trials. In the USA and the EU, the pre\u2010CVOT indication on all 14 labels was \u201cimprovement in glycaemic control\u201d. Six drugs showed significant cardiovascular risk reduction, which led to an additional indication regarding reduction of cardiovascular adverse events in the USA, and a change to the EU indication to specify treatment of adults with T2D. The initial indication in Japan, T2D, remained unchanged. Regarding safety, significant increases in heart failure were observed only in the saxagliptin trial. A warning was added to the saxagliptin labels in the EU and Japan, whereas the FDA required a class effect warning to be added to the labels of all 4 dipeptidyl peptidase\u20104 inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Regulatory authorities using identical trial data made substantially different decisions regarding both safety and efficacy of hypoglycaemic drugs. The differences in initial indication wording between Japan and the other authorities suggest that trial data and T2D are interpreted differently in these regions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14814","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T11:31:54Z","timestamp":1615462314000},"page":"3938-3948","source":"Crossref","is-referenced-by-count":0,"title":["Approvals of type 2 diabetes drugs tested in cardiovascular outcome trials: A tripartite comparison"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8326-8835","authenticated-orcid":false,"given":"Rumiko","family":"Shimazawa","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Tokai University School of Medicine Isehara  Kanagawa 259\u20101193 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5157-1362","authenticated-orcid":false,"given":"Masayuki","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics Kagawa University Hospital  Miki\u2010cho Kagawa 761\u20100793 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,31]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"International Diabetes Federation.IDF Diabetes Atlas 9th edition 2019.https:\/\/diabetesatlas.org\/en\/sections\/worldwide-toll-of-diabetes.html. 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