{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T20:54:45Z","timestamp":1790456085353,"version":"4.1.0"},"reference-count":75,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,4,6]],"date-time":"2016-04-06T00:00:00Z","timestamp":1459900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"South Texas Veterans Administration Health Care System"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:p>\n                    The recently completed\n                    <jats:styled-content style=\"fixed-case\">EMPA\u2010REG<\/jats:styled-content>\n                    study showed that empagliflozin significantly decreased the major adverse cardiac events (\n                    <jats:styled-content style=\"fixed-case\">MACE<\/jats:styled-content>\n                    ) endpoint, which comprised cardiovascular death, non\u2010fatal myocardial infarction (\n                    <jats:styled-content style=\"fixed-case\">MI<\/jats:styled-content>\n                    ) and stroke, in patients with high\u2010risk type 2 diabetes (\n                    <jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content>\n                    ), primarily through a reduction in cardiovascular death, without a significant decrease in either\n                    <jats:styled-content style=\"fixed-case\">MI<\/jats:styled-content>\n                    or stroke. In the\n                    <jats:styled-content style=\"fixed-case\">PROactive<\/jats:styled-content>\n                    study, pioglitazone decreased the\n                    <jats:styled-content style=\"fixed-case\">MACE<\/jats:styled-content>\n                    endpoint by a similar degree to that observed in the\n                    <jats:styled-content style=\"fixed-case\">EMPA\u2010REG<\/jats:styled-content>\n                    study, through a marked reduction in both recurrent\n                    <jats:styled-content style=\"fixed-case\">MI<\/jats:styled-content>\n                    and stroke and a modest reduction in cardiovascular death. These observations suggest that pioglitazone might be an ideal agent to combine with empagliflozin to further reduce cardiovascular events in patients with high\u2010risk diabetes as empagliflozin also promotes salt\/water loss and would be expected to offset any fluid retention associated with pioglitazone therapy. In the present paper, we provide an overview of the potential benefits of combined pioglitazone\/empagliflozin therapy to prevent cardiovascular events in patients with\n                    <jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/dom.12652","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T03:58:41Z","timestamp":1456459121000},"page":"454-462","source":"Crossref","is-referenced-by-count":51,"title":["Revitalization of pioglitazone: the optimum agent to be combined with a sodium\u2010glucose co\u2010transporter\u20102 inhibitor"],"prefix":"10.1111","volume":"18","author":[{"given":"R. A.","family":"DeFronzo","sequence":"first","affiliation":[{"name":"Diabetes Division University of Texas Health Science Center and Texas Diabetes Institute  San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Chilton","sequence":"additional","affiliation":[{"name":"Cardiology Division University of Texas Health Science Center and Texas Diabetes Institute  San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Norton","sequence":"additional","affiliation":[{"name":"Diabetes Division University of Texas Health Science Center and Texas Diabetes Institute  San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Diabetes Division and Department of Radiology University of Texas Health Science Center and Texas Diabetes Institute  San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. E. J.","family":"Ryder","sequence":"additional","affiliation":[{"name":"Diabetes and Endocrine Unit City Hospital  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Abdul\u2010Ghani","sequence":"additional","affiliation":[{"name":"Diabetes Division University of Texas Health Science Center and Texas Diabetes Institute  San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2011.08.107"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)07019-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0806470"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60447-5"},{"key":"e_1_2_9_7_1","unstructured":"The Seventh Report of the Joint National Committee on Prevention Detection Evaluation and Treatment of High Blood Pressure. Available from URL:http:\/\/www.nhlbi.nih.gov\/files\/docs\/guidelines\/jnc7full.pdf. Accessed 10 March 2016."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2010-0029"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01406.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.595496"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.089078"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17018-9"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67528-9"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2008.03.002"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12608"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.10.1180"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.296.21.joc60158"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.299.13.1561"},{"key":"e_1_2_9_19_1","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMoa1506930","article-title":"Pioglitazone after ischemic stroke or transient ischemic attack","author":"Kernan WN","year":"2016","journal-title":"N Engl J Med"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009492"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b4731"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1278"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.29.03.06.dc05-2004"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.23.11.1605"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/08037050600853720"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2009.02025.x"},{"key":"e_1_2_9_27_1","first-page":"A2","article-title":"Improved left ventricular diastolic function (LVDF) following pioglitazone therapy is strongly related to increased myocardial insulin sensitivity","volume":"63","author":"Clarke GD","year":"2014","journal-title":"Diabetes"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041001"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-9028"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1684-1"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc05-2445"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90960.2008"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.164.19.2097"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000090521.25968.4D"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.7.1547"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-1256-9"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00551.2006"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI70704"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-3472"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72227"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0265"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa066224"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-2364"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2015.1114098"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.25.3.517"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.K05-067"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-1693"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2015.05.511"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12188"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12273"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116851"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2015.05.002"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2010.01314.x"},{"key":"e_1_2_9_54_1","unstructured":"WeinsteinJ.Empagliflozin and renal outcomes: further insights into the renal protection of SGLT2 inhibitors.0000. Available from URL:http:\/\/ukidney.com\/news\/entry\/empagliflozin&#x02010;and&#x02010;renal&#x02010;outcomes&#x02010;further&#x02010;insights&#x02010;in&#x02010;to&#x02010;the&#x02010;renal&#x02010;protection&#x02010;of&#x02010;sglt2&#x02010;inhibitors. Accessed 10 March 2016."},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12459"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1159\/000364909"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00418.x"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1997.272.6.E989"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2009.11.013"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002516"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-012-0275-6"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0843"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP161292.PS"},{"key":"e_1_2_9_64_1","unstructured":"Pioglitazone (marketed as Actos AM and Duetact) information [Internet]. Available from URL:http:\/\/www.fda.gov\/drugs\/drugsafety\/postmarketdrugsafetyinformationforpatientsandproviders\/ucm109136.htm. Accessed 10 March 2016."},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0899"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.6.8567"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0911"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2010.03187.x"},{"key":"e_1_2_9_69_1","unstructured":"Takeda Pharmaceuticals North America.Actos (pioglitazone)2007. Available from URL:http:\/\/www.fda.gov\/safety\/medwatch\/safetyinformation\/safetyalertsforhumanmedicalproducts\/ucm150451.htmAccessed 10 March 2016."},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200932070-00001"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.080486"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.1090003"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2012.01630.x"},{"key":"e_1_2_9_74_1","unstructured":"Takeda Press Release. Available from URL:http:\/\/www.takeda.com\/news\/2014\/20140829_6714.htmlAccessed 10 March 2016."},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3456-9"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-015-0128-9"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.12652","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.12652","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.12652","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T01:23:45Z","timestamp":1761873825000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.12652"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,6]]},"references-count":75,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,5]]}},"alternative-id":["10.1111\/dom.12652"],"URL":"https:\/\/doi.org\/10.1111\/dom.12652","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,6]]}}}