New Haven, CT—Sodium-glucose cotransporter 2 (SGLT2) inhibitors are showing promise to prevent or slow the onset of type 2 diabetes (T2D) in patients with heart failure.

A presentation at the American Diabetes Association’s 80th Scientific Sessions discussed how dapagliflozin treatment of patients in the DAPA-HF trial reduced relative incidence of new-onset diabetes by one-third over a median follow-up period of 18 months. Those results came from a prespecified analysis of the multicenter trial that included 2,605 heart failure patients without diabetes at baseline.

The Yale University School of Medicine–led study was an analysis of the original DAPA-HF trial, which was a phase lll placebo-controlled international study of dapagliflozin in chronic heart failure patients with reduced ejection fraction.

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. Results indicated the risk of worsening heart failure or death from cardiovascular events was reduced more among the patients receiving dapagliflozin than among those who received the placebo, with no regard to whether or not they also had diabetes.

The question addressed in the analysis was whether dapagliflozin reduced the incidence of T2D in the 2,605 trial participants who did not already have diabetes. New-onset T2D was defined as hemoglobin A1C of 6.5% or greater on two consecutive study visits throughout the median 18.2-month follow-up.

Results of the analysis include:
• 157 participants developed T2D, 150 of whom had prediabetes (A1C 5.7%-6.4%) at the beginning of the study.
• Patients who developed T2D had higher average A1C levels, greater body mass index and lower eGFR kidney function levels at the beginning of the study than those who did not develop diabetes.
• Analysis reveals that 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 developed 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,” explained lead investigator Silvio Inzucchi, MD, 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.”
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