{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T16:44:47Z","timestamp":1794242687789,"version":"4.9.0"},"reference-count":26,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>In prespecified analyses, the treatment effect for major adverse cardiovascular event (MACE) of tirzepatide compared with imputed placebo was estimated using SURPASS-Cardiovascular Outcomes Trial (SURPASS-CVOT) and Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) trial data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>The indirect comparison with placebo was conducted for primary (MACE-3) and secondary outcomes of SURPASS-CVOT. The analysis included data from REWIND participants who would have been eligible for SURPASS-CVOT and all participants from SURPASS-CVOT. Propensity score estimation was used to adjust for differences in participant characteristics between studies. The indirect analysis of the treatment effect was derived by multiplying the hazard ratio (HR) for MACE-3 between tirzepatide and dulaglutide in SURPASS-CVOT by the HR for dulaglutide versus placebo in REWIND. Sensitivity analyses were performed using unadjusted analyses, including both the selected REWIND and the entire REWIND populations, and adjusted analysis in the entire REWIND population. Post hoc sensitivity analyses used data from a recent glucagon-like peptide 1 receptor agonist (GLP-1RA) meta-analysis that included REWIND.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Analyses included 2,055 of 9,901 participants from REWIND and all 13,165 participants from SURPASS-CVOT. In indirect treatment effect comparisons, tirzepatide versus placebo was associated with lower MACE-3 (HR 0.72; 95% CI 0.55, 0.94), death from CV cause or heart failure events (HR 0.70; 95% CI 0.51, 0.96), and all-cause death (HR 0.61; 95% CI 0.45, 0.82). Sensitivity analyses, including nonadjusted or the entire REWIND cohort data or meta-analysis data for GLP-1RAs, were generally consistent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>In this indirect prespecified exploratory comparison, tirzepatide compared with imputed placebo was associated with reduced CV outcomes and all-cause mortality in participants with type 2 diabetes and established atherosclerotic CV disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title\/>\n                  <\/jats:sec>","DOI":"10.2337\/dc26-0298","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T14:12:47Z","timestamp":1775484767000},"page":"1771-1778","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":19,"title":["Estimating the True MACE Benefits From Tirzepatide in SURPASS-CVOT Using an Imputed Placebo Analysis of REWIND"],"prefix":"10.2337","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1604-2593","authenticated-orcid":false,"given":"Naveed","family":"Sattar","sequence":"first","affiliation":[{"name":"School of Cardiovascular Medicine and Metabolic Health, University of Glasgow 1 , Glasgow, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8072-2836","authenticated-orcid":false,"given":"Hertzel C.","family":"Gerstein","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University and Hamilton Health Sciences 2 , Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"D\u2019Alessio","sequence":"additional","affiliation":[{"name":"Duke University Medical Center 3 , Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai 4 , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Buse","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill 5 , Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5388-0270","authenticated-orcid":false,"given":"Stefano","family":"Del Prato","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Center \u201cHealth Science\u201d, Sant\u2019Anna School of Advanced Studies 6 , Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Kahn","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington 7 , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Michael","family":"Lincoff","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University 8 , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6412-7989","authenticated-orcid":false,"given":"Darren K.","family":"McGuire","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center and Parkland Health and Hospital System 9 , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5749-6954","authenticated-orcid":false,"given":"Michael A.","family":"Nauck","sequence":"additional","affiliation":[{"name":"Diabetes, Endocrinology and Metabolism Section, Department of Medicine, St. Josef-Hospital, Katholisches Klinikum Bochum gGmbH, Ruhr University of Bochum 10 , Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Nissen","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Coordinating Center for Clinical Research and Department of Medicine, Cleveland Clinic 11 , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0041-1876","authenticated-orcid":false,"given":"Bernard","family":"Zinman","sequence":"additional","affiliation":[{"name":"University of Toronto, Lunenfeld-Tanenbaum Research Institute and Mount Sinai Hospital 12 , Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2672-0949","authenticated-orcid":false,"given":"Sophia","family":"Zoungas","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University 13 , Melbourne, 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post-hoc analysis of an open-label, randomised, phase 3 trial","volume":"10","author":"Heerspink","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2026100621432332700_B6","doi-asserted-by":"crossref","first-page":"110770","DOI":"10.1016\/j.diabres.2023.110770","article-title":"Perspectives on weight control in diabetes - tirzepatide","volume":"202","author":"V\u00e1rkonyi","year":"2023","journal-title":"Diabetes Res Clin Pract"},{"key":"2026100621432332700_B7","doi-asserted-by":"crossref","first-page":"A16779","DOI":"10.1161\/circ.148.suppl_1.16779","article-title":"Tirzepatide reduces high-sensitivity C-reactive protein in patients with type 2 diabetes and high cardiovascular risk: a post hoc analysis of the SURPASS-4 Trial","volume":"148","author":"Bhatt","year":"2023","journal-title":"Circulation"},{"key":"2026100621432332700_B8","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/s41591-022-01707-4","article-title":"Tirzepatide cardiovascular event 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A study of tirzepatide (LY3298176) compared with dulaglutide on major cardiovascular events in participants with type 2 diabetes (SURPASS-CVOT)\n          . In: ClinicalTrials.gov. Bethesda, MD, National Library of Medicine, 2025. NLM Identifier: NCT04255433. Accessed 23 March 2026. 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