<b>Objective </b>
<p>The SGLT2 inhibitor
dapagliflozin reduced the risk of cardiovascular mortality and worsening heart
failure in the <a>Dapagliflozin and Prevention of Adverse-Outcomes in Heart
Failure </a>trial (DAPA-HF). This report explores the effect of
dapagliflozin on incident type 2 diabetes in the non-diabetic cohort enrolled
in the trial.</p>
<p><b> </b></p>
<p><b>Research Design/Methods</b></p>
<p>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.</p>
<p><b> </b></p>
<p><b>Results</b></p>
<p>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.</p>
<p><b>Conclusions</b></p>
<p>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.</p>
Insulin ameliorates exercise ventilatory efficiency and oxygen uptake in patients with heart failure–type 2 diabetes comorbidity
