Dapagliflozin and the incidence of type 2 diabetes in patients with heart failure and reduced ejection fraction: an exploratory analysis from DAPA-HF

Inzucchi, S. E. et al. (2021) Dapagliflozin and the incidence of type 2 diabetes in patients with heart failure and reduced ejection fraction: an exploratory analysis from DAPA-HF. Diabetes Care, 44(2), pp. 586-594. (doi: 10.2337/dc20-1675) (PMID:33355302)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Docherty, Dr Kieran and McMurray, Professor John and Jhund, Professor Pardeep and Kober, Professor Lars
• Authors: Inzucchi, S. E., Docherty, K. F., Køber, L., Kosiborod, M. N., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Solomon, S. D., Verma, S., Bělohlávek, J., Böhm, M., Chiang, C.-E., de Boer, R. A., Diez, M., Dukát, A., Ljungman, C. E.A., Bengtsson, O., Langkilde, A. M., Sjöstrand, M., Jhund, P. S., and McMurray, J. J.V.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Diabetes Care
• Publisher: American Diabetes Association
• ISSN: 0149-5992
• ISSN (Online): 1935-5548
• Published Online: 18 December 2020
• Copyright Holders: Copyright © 2020 American Diabetes Association
• First Published: First published in Diabetes Care 44(2):586-594
• Publisher Policy: Reproduced in accordance with the publisher copyright policy