Dapagliflozin Reduces Incident T2D in Patients with HFrEF

CHICAGO (June 15, 2020) — The SGLT2 inhibitor dapagliflozin prevented incident type 2 diabetes (T2D) in patients with heart failure (HF), according to results of the study titled “Effect of dapagliflozin on the incidence of diabetes: A prespecified exploratory analysis from DAPA-HF," presented today at the American Diabetes Association’s80th Virtual Scientific Sessions.

The original DAPA-HF trial was a phase 3 placebo-controlled international study of dapagliflozin (Farxiga, AstraZeneca) in people with chronic heart failure and a reduced ejection fraction (HFrEF). The trial enrolled people both with and without T2D. The 4,774 study participants, average age 66 years, were randomly assigned to take either 10 mg of dapagliflozin or a placebo once daily and were followed for 18.2 months.

Silivio Inzucchi, MD, Professor of Medicine, Yale University School of Medicine.

The study found the risk of worsening HF or death from cardiovascular causes was lower among patients treated with dapagliflozin than those who received the placebo, regardless of the presence or absence of T2D.

The current planned analysis assessed whether dapagliflozin reduced the incidence of T2D in the 2,605 trial participants who did not have T2D when the study began.

Of the participants without T2D, 1,298 had been assigned to the dapagliflozin group, and 1,307 to the placebo group. New-onset T2D was defined as A1c ≥ 6.5% on two consecutive study visits throughout the median 18.2-month follow-up.

Results

• A total of 157 participants developed T2D, 150 of whom had prediabetes (A1c 5.7-6.4%) at the beginning of the study.
  
• The people who developed T2D had higher average A1c levels, greater body mass index and lower eGFR at the beginning of the study than those who did not develop diabetes.
  
• Cox proportional hazards model data showed dapagliflozin reduced new-onset diabetes by 32%, with 4.9% of dapagliflozin patients (64 of 1,298) developing T2D, compared to 7.1% (93 of 1,307) in the placebo group.
  
  In an additional exploratory analysis, those patients who did develop diabetes during the trial experienced a 70% increase in mortality, after adjustments for baseline features.

“Our sub-study within the DAPA-HF trial demonstrates that diabetes prevention could be considered an additional benefit of dapagliflozin, whose main effect, of course is to reduce cardiovascular mortality and worsening heart failure in patients with heart failure and reduced ejection fraction,” said Silvio Inzucchi, MD, lead investigator and professor of medicine at the Yale University School of Medicine.

“The 32% relative risk reduction compares favorably with the 31% reduction with metformin, as reported in the Diabetes Prevention Program. We will need to do more studies to see if this effect extends to patients without heart failure and reduced ejection fraction and to evaluate how durable the benefit might be and how long diabetes prevention persists after the discontinuation of therapy.”