OBJECTIVE: The sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of cardiovascular mortality and worsening heart failure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. This report explores the effect of dapagliflozin on incident type 2 diabetes (T2D) in the cohort without diabetes enrolled in the trial. RESEARCH DESIGN AND METHODS: The subgroup of 2,605 patients with heart failure and reduced ejection fraction (HFrEF), no prior history of diabetes, and an HbA1c of <6.5% at baseline was randomized to dapagliflozin 10 mg daily or placebo. In this exploratory analysis, surveillance for new-onset diabetes was accomplished through periodic HbA1c testing as part of the study protocol and comparison between the treatment groups assessed through a Cox proportional hazards model. RESULTS: At baseline, the mean HbA1c was 5.8%. At 8 months, there were minimal changes, with a placebo-adjusted change in the dapagliflozin group of -0.04%. Over a median follow-up of 18 months, diabetes developed in 93 of 1,307 patients (7.1%) in the placebo group and 64 of 1,298 (4.9%) in the dapagliflozin group. Dapagliflozin led to a 32% reduction in diabetes incidence (hazard ratio 0.68, 95% CI 0.50-0.94; P = 0.019). More than 95% of the participants who developed T2D had prediabetes at baseline (HbA1c 5.7-6.4%). Participants who developed diabetes in DAPA-HF had a higher subsequent mortality than those who did not. CONCLUSIONS: In this exploratory analysis among patients with HFrEF, treatment with dapagliflozin reduced the incidence of new diabetes. This potential benefit needs confirmation in trials of longer duration and in people without heart failure.

2nd Department of Medicine Cardiovascular Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

5th Department of Internal Medicine Comenius University in Bratislava Bratislava Slovakia

AstraZeneca Gothenburg Sweden

BHF Cardiovascular Research Centre University of Glasgow Glasgow U K

Cardiovascular Division Brigham and Women's Hospital and Harvard Medical School Boston MA

Department of Cardiology University of Groningen University Medical Center Groningen Groningen the Netherlands

Department of Molecular and Clinical Medicine and Cardiology Sahlgrenska Academy Gothenburg Sweden

Division of Cardiac Surgery St Michael's Hospital University of Toronto Toronto Ontario Canada

Division of Cardiology Instituto Cardiovascular de Buenos Aires Buenos Aires Argentina

General Clinical Research Center and Division of Cardiology Taipei Veterans General Hospital and National Yang Ming University Taipei Taiwan

Internal Medicine Clinic 3 Saarland University Medical Center Homburg Saar Germany

National University of Cordoba Cordoba Argentina

Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Saint Luke's Mid America Heart Institute and University of Missouri Kansas City Kansas City MO

Section of Endocrinology Yale University School of Medicine New Haven CT

TIMI Study Group Cardiovascular Division Brigham and Women's Hospital and Harvard Medical School Boston MA

Wroclaw Medical University Wroclaw Poland

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See more in PubMed

figshare
10.2337/figshare.13235543

ClinicalTrials.gov
NCT03036124