AIMS: People with diabetes are at high risk for cardiovascular events including heart failure (HF). We examined the effect of the glucagon-like peptide 1 agonist dulaglutide on incident HF events and other cardiovascular outcomes in those with or without prior HF in the randomized placebo-controlled Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial. METHODS AND RESULTS: The REWIND major adverse cardiovascular event (MACE) outcome was the first occurrence of a composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes). In this post-hoc analysis, a HF event was defined as an adjudication-confirmed hospitalization or urgent evaluation for HF. Of the 9901 participants studied over a median follow-up of 5.4 years, 213/4949 (4.3%) randomly assigned to dulaglutide and 226/4952 (4.6%) participants assigned to placebo experienced a HF event (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.77-1.12; p = 0.456). In the 853 (8.6%) participants with HF at baseline, there was no change in either MACE or HF events with dulaglutide as compared to participants without HF (p = 0.44 and 0.19 for interaction, respectively). Combined cardiovascular death and HF events were marginally reduced with dulaglutide compared to placebo (HR 0.88, 95% CI 0.78-1.00; p = 0.050) but unchanged in patients with and without HF at baseline (p = 0.31). CONCLUSIONS: Dulaglutide was not associated with a reduction in HF events in patients with type 2 diabetes regardless of baseline HF status over 5.4 years of follow-up.

Baker Heart and Diabetes Institute Melbourne Victoria Australia

Department of Medicine K2 Karolinska Institute Stockholm Sweden

Division of Endocrinology and Metabolism Taipei Veterans General Hospital Taipei Taiwan

Division of Endocrinology University of Cape Town Cape Town South Africa

Eli Lilly and Co Indianapolis IN USA

Endocrinology and Nutrition Department Hospital Clínic i Universitari Barcelona Spain

Institut Universitaire de Cardiologie et Pneumologie de Québec Université Laval Québec City Québec Canada

International Research Center Hospital Alemão Oswaldo Cruz São Paulo Brazil

Li Ka Shing Knowledge Institute St Michael's Hospital University of Toronto Toronto Ontario Canada

Medical University of South Carolina Ralph H Johnson VA Medical Center Charleston SC USA

National Medical Research Center of Cardiology Moscow Russia

Population Health Research Institute Hamilton Health Sciences and McMaster University Hamilton Ontario Canada

Robert Koch Medical Center Sofia Bulgaria

St John's Research Institute Bangalore India

Universidad de La Fontera Temuco Chile

University Hospital Motol Prague Czech Republic

University of Tennessee Health Science Center Memphis TN USA

University of Washington Heart Institute Seattle WA USA

Eur J Heart Fail. 2022 Oct;24(10):1813-1815. doi: 10.1002/ejhf.2693. PubMed

Eur J Heart Fail. 2022 Nov;24(11):2207. doi: 10.1002/ejhf.2694. PubMed

Eur J Heart Fail. 2022 Nov;24(11):2207-2208. doi: 10.1002/ejhf.2719. PubMed

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