Evidence map›Paper›PMID 41940793›Full record

Trial reportDiabetes care2026

Estimating the True MACE Benefits From Tirzepatide in SURPASS-CVOT Using an Imputed Placebo Analysis of REWIND.

Naveed Sattar, Hertzel C Gerstein, David D'Alessio, Deepak L Bhatt, John B Buse, Stefano Del Prato, Steven E Kahn, A Michael Lincoff, Darren K McGuire, Michael A Nauck and 11 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetes care, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Naveed SattarSchool of Cardiovascular Medicine and Metabolic Health, University of Glasgow, Glasgow, U.K.ORCID 0000-0002-1604-2593
Hertzel C GersteinPopulation Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.ORCID 0000-0001-8072-2836
David D'AlessioDuke University Medical Center, Durham, NC.
Deepak L BhattMount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY.
John B BuseUniversity of North Carolina at Chapel Hill, Chapel Hill, NC.
Stefano Del PratoInterdisciplinary Research Center "Health Science", Sant'Anna School of Advanced Studies, Pisa, Italy.ORCID 0000-0002-5388-0270
Steven E KahnDivision of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, WA.
A Michael LincoffDepartment of Cardiovascular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH.
Darren K McGuireUniversity of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas, TX.ORCID 0000-0002-6412-7989
Michael A NauckDiabetes, Endocrinology and Metabolism Section, Department of Medicine, St. Josef-Hospital, Katholisches Klinikum Bochum gGmbH, Ruhr University of Bochum, Bochum, Germany.ORCID 0000-0002-5749-6954
Steven E NissenCleveland Clinic Coordinating Center for Clinical Research and Department of Medicine, Cleveland Clinic, Cleveland, OH.
Bernard ZinmanUniversity of Toronto, Lunenfeld-Tanenbaum Research Institute and Mount Sinai Hospital, Toronto, Ontario, Canada.ORCID 0000-0002-0041-1876
Sophia ZoungasSchool of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.ORCID 0000-0003-2672-0949
Amy BarteeEli Lilly and Company, Indianapolis, IN.
Debra MillerEli Lilly and Company, Indianapolis, IN.
Hiroshi NishiyamaEli Lilly and Company, Indianapolis, IN.
Yongming QuEli Lilly and Company, Indianapolis, IN.
Govinda WeerakkodyEli Lilly and Company, Indianapolis, IN.
Russell J WieseEli Lilly and Company, Indianapolis, IN.ORCID 0009-0007-6705-7545
Imre PavoEli Lilly and Company, Indianapolis, IN.
Stephen J NichollsVictorian Heart Institute, Monash University, Melbourne, Australia.ORCID 0000-0002-9668-4368

Funding

Eli Lilly and Company
6 · The paper itself

Abstract

objectiveIn 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. RESEARCH DESIGN AND

methodsThe 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.

resultsAnalyses 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.

conclusionsIn 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.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Glucagon-Like PeptidesHypoglycemic AgentsImmunoglobulin Fc FragmentsRecombinant Fusion ProteinsAgedFemaleHumansMaleMiddle AgedTirzepatidedulaglutideGlucagon-Like PeptidesHypoglycemic AgentsImmunoglobulin Fc FragmentsRecombinant Fusion ProteinsTirzepatide

Identifiers

PMID41940793
PMCPMC13594787

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.