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Dapagliflozin and the Incidence of Type 2 Diabetes in Patients With Heart Failure and Reduced Ejection Fraction: An Exploratory Analysis From DAPA-HF

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posted on 21.12.2020, 07:17 by Silvio E Inzucchi, Kieran F Docherty, Lars Køber, Mikhail N Kosiborod, Felipe A Martinez, Piotr Ponikowski, Marc S Sabatine, Scott D Solomon, Subodh Verma, Jan Bělohlávek, Michael Böhm, Chern-En Chiang, Rudolf A. de Boer, Mirta Diez, Andre Dukát, Charlotta E.A. Ljungman, Olof Bengtsson, Anna Maria Langkilde, Mikaela Sjöstrand, Pardeep S Jhund, John JV McMurray, DAPA-HF Investigators and Committees
Objective

The SGLT2 inhibitor dapagliflozin reduced the risk of cardiovascular mortality and worsening heart failure in the Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure trial (DAPA-HF). This report explores the effect of dapagliflozin on incident type 2 diabetes in the non-diabetic cohort enrolled in the trial.

Research Design/Methods

The subgroup of 2605 patients with heart failure and reduced ejection fraction (HFrEF), no prior history of diabetes, and a 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 93/1307 patients (7.1%) in the placebo group and 64/1298 (4.9%) in the dapagliflozin group. Dapagliflozin led to a 32% reduction in diabetes incidence (HR 0.68, 95% CI, 0.50-0.94; p=0.019.) More than 95% of the participants who developed type 2 diabetes 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.

Funding

DAPA-HF was supported by Astra-Zeneca.

History