{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:16:42Z","timestamp":1789186602774,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"4","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:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008349","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008349","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":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The sodium\u2010glucose co\u2010transporter 2 inhibitor empagliflozin reduced the total burden of cardiovascular, mortality, and all\u2010cause hospitalization events, including first and recurrent events, in EMPA\u2010REG OUTCOME participants with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD). We investigated the effect of empagliflozin on the total burden of cardiovascular and hospitalization events in Asian participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Participants were randomized to empagliflozin 10 mg, 25\u2009mg or placebo plus standard of care. The primary and key secondary outcomes were the composite of cardiovascular death, non\u2010fatal myocardial infarction, and non\u2010fatal stroke and the primary outcome plus hospitalization for unstable angina, respectively. The effect of pooled empagliflozin versus placebo on total (first plus recurrent) cardiovascular and hospitalization events was analysed using a negative binomial model that preserves randomization and accounts for within\u2010patient correlation of multiple events. We analysed Asian versus non\u2010Asian EMPA\u2010REG OUTCOME population subgroups post hoc.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 1517 Asian participants, empagliflozin reduced the relative risk of total events of the primary outcome by 39% versus placebo [rate ratio (95% confidence interval): 0.61 (0.43, 0.89)], the key secondary outcome by 33% [0.67 (0.48, 0.93)], the composite of cardiovascular death (excluding fatal stroke) and hospitalization for heart failure by 43% [0.57 (0.33, 0.996)], and all\u2010cause hospitalization by 21% [0.79 (0.65, 0.97)]. The effects of empagliflozin were consistent between Asian and non\u2010Asian populations (treatment\u2010by\u2010subgroup interaction\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&gt;\u2009.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Empagliflozin reduced the total burden of cardiovascular and hospitalization events in Asian and non\u2010Asian EMPA\u2010REG OUTCOME participants with T2D and established ASCVD, consistent with the overall trial population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14626","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T23:39:48Z","timestamp":1639525188000},"page":"662-674","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The effect of empagliflozin on the total burden of cardiovascular and hospitalization events in the Asian and\n                    <scp>non\u2010Asian<\/scp>\n                    populations of the\n                    <scp>EMPA\u2010REG OUTCOME<\/scp>\n                    trial of patients with type 2 diabetes and cardiovascular disease"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1574-0565","authenticated-orcid":false,"given":"Kohei","family":"Kaku","sequence":"first","affiliation":[{"name":"Department of General Internal Medicine Kawasaki Medical School General Medical Center  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Wanner","sequence":"additional","affiliation":[{"name":"W\u00fcrzburg University Clinic  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology (CVK); and Berlin Institute of Health Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) Partner Site Berlin Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Pocock","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics London School of Hygiene &amp; Tropical Medicine  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4903-7210","authenticated-orcid":false,"given":"Atsutaka","family":"Yasui","sequence":"additional","affiliation":[{"name":"Medical Division Nippon Boehringer Ingelheim Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Mattheus","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Ingelheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren S.","family":"Lund","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH  Ingelheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32279-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12098"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2012.06838.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.2696"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14074"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.2.231"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.23.12.1774"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2010.10.016"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.04.036"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-022972"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.790048"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000090348.52943.A2"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-016-1422-x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ihj.2016.02.022"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69703-1"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.726"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12699"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12910"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-16-1148"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.033065"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(20)30344-2"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2020.108488"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-0719"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S193528"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1989.10478873"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.7326\/M21-0651"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-0573"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14415"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2021.1898585"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(21)02828-X"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(21)01901-X"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.14626","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.14626","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.14626","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:18:50Z","timestamp":1761862730000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.14626"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,9]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1111\/dom.14626"],"URL":"https:\/\/doi.org\/10.1111\/dom.14626","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,9]]},"assertion":[{"value":"2021-09-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}