Treatment with the sodium-glucose cotransporter-2 (SGLT-2) inhibitor dapagliflozin for heart failure (HF) may help prevent the onset of type 2 diabetes (T2D), according to a planned exploratory analysis of the DAPA-HF trial. "While the major role of dapagliflozin in patients with heart failure with reduced ejection fraction is to reduce cardiovascular mortality and worsening heart failure, decreasing the incidence of type 2 diabetes may be considered an additional benefit, especially since incident diabetes is associated with greater mortality," said lead researcher Dr. Silvio Inzucchi of Yale University School of Medicine, in New Haven, Connecticut, in presenting the findings at the American Diabetes Association (ADA) 2020 virtual scientific sessions. SGLT-2 inhibitors were originally developed to treat type 2 diabetes. "DAPA-HF is the first trial to demonstrate a diabetes prevention effect from an SGLT-2 inhibitor," Dr. Inzucchi said. In the original DAPA-HF trial, 4,744 adults with HF and reduced ejection fraction, with or without T2D, were randomly assigned to take either 10 mg of dapagliflozin or placebo once daily. Dapagliflozin reduced the risk for worsening HF and cardiovascular death by 26% over a median of 18.2 months The planned exploratory analysis focused on patients in the trial who did not have T2D at baseline. Of these, 1,298 were in the dapagliflozin group, and 1,307 in the placebo group. New-onset T2D was defined as hemoglobin (Hb)A1C at or above 6.5% on two consecutive visits during follow-up. Altogether, 157 people developed T2D, most of whom had pre-diabetes at baseline (HbA1C of 5.7% to 6.4%). Individuals who developed T2D had higher average HbA1C levels, greater BMI and lower level of kidney function than those who did not develop T2D. Treatment with dapagliflozin reduced the risk of T2D onset by 32% (HR 0.68; 95% CI 0.50 to 0.94; 4.9% of patients in the dapagliflozin arm developed T2D during follow-up, compared with 7.1% in the placebo arm. In an additional exploratory analysis, compared with individuals who did not develop T2D during the trial, those that did had a 70% increased risk of dying from any cause, after adjustment for baseline features. "Dapagliflozin is the first medication demonstrated to reduce both incident T2D and mortality in a single trial," Dr. Inzucchi said. The DAPA-HF trial was sponsored by AstraZeneca, which makes dapagliflozin. Dr. Inzucchi has financial relationships with the company. —Megan Brooks Source
