DAPA-HF: Dapagliflozin reduces new-onset diabetes among adults with heart failure
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Adults with heart failure assigned the SGLT2 inhibitor dapagliflozin had a 32% lower risk for new-onset type 2 diabetes over 18 months of follow-up vs. placebo, according to a planned analysis of DAPA-HF trial data.
“DAPA-HF is the first trial to demonstrate a diabetes prevention effect from an SGLT2 inhibitor, in contrast to other diabetes prevention trials with glucose-lowing medications,”
Silvio E. Inzucchi, MD, professor of medicine (endocrinology) at Yale University School of Medicine and Yale-New Haven Hospital, said during a presentation at the virtual American Diabetes Association Scientific Sessions. “Dapagliflozin is the first medication demonstrated to reduce both incident type 2 diabetes and mortality in a single trial, although obviously we have not necessarily linked those two effects of the drug.”
As Healio previously reported, DAPA-HF included 4,744 adults with heart failure with reduced ejection fraction (HFrEF) who were randomly assigned to continue their standard care plus once-daily dapagliflozin 10 mg (Farxiga, AstraZeneca) or placebo. Dapagliflozin reduced risk for worsening heart failure and cardiovascular death by 26% during a median of 18.2 months for participants with and without diabetes at baseline.
Among the 55% of participants (n = 2,605) who did not have diabetes at baseline, defined as HbA1c less than 6.5% at the first two study visits, 1,748 (mean age, 67 years; 75.3% men; mean BMI, 27.4 kg/m2; mean HbA1c, 6%) had prediabetes, and 857 had normal glucose levels (mean age, 64.5 years; 76.7% men; mean BMI, 26.8 kg/m2; mean HbA1c, 5.3%). During the trial, 157 participants developed type 2 diabetes — 95.5% of them with prediabetes defined as HbA1c between 5.7% and 6.4%, and 86.6% with prediabetes defined as HbA1c between 6% and 6.4%, at baseline. In addition to higher baseline HbA1c, those who developed diabetes also had higher mean baseline BMI (28.5 kg/m2 vs. 27.1 kg/m2; P = .003) and lower mean estimated glomerular filtration rate (61.5 mL/min/1.73 m2 vs. 68.2 mL/min/1.73 m2; P < .001) vs. those who did not develop diabetes.
The incidence of new-onset diabetes was 4.9% in the dapagliflozin group vs. 7.1% in the placebo group, for a 32% reduction in risk with dapagliflozin (HR = 0.68; 95% CI, 0.5-0.94).
In an exploratory analysis to assess whether new-onset diabetes was associated with CV outcomes, data showed a 70% increased risk for all-cause mortality (adjusted HR = 1.7; 95% CI, 1.04-2.8) and a 77% increased risk for CV death (aHR = 1.77; 95% CI, 1.04-3.02) vs. those who did not develop diabetes.
“While the major role of dapagliflozin in patients with HFrEF 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,” Inzucchi said.
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Inzucchi SE, et al. 271-OR. Presented at: American Diabetes Association Scientific Sessions; June 12-16, 2020; (virtual meeting).
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