medwireNews: The sodium-glucose cotransporter (SGLT)2 inhibitor dapagliflozin reduces the risk for type 2 diabetes by a third in people with heart failure with reduced ejection fraction (HFrEF), particularly those with prediabetes, shows an analysis of data from the DAPA-HF trial.
Speaking at the virtual ADA 80th Scientific Sessions, Silvio Inzucchi (Yale University School of Medicine, New Haven, Connecticut, USA) said that “DAPA-HF is the first trial to demonstrate a ‘diabetes prevention’ effect from an SGLT2 inhibitor.”
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In a statement to the press he added: “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.”
The original DAPA-HF trial, previously reported by medwireNews, included 4744 patients with HFrEF who were followed up for a median 18.2 months after random assignment to treatment with dapagliflozin 10 mg/day or placebo.
The current analysis focused on the 2605 (55%) participants who did not have diabetes at baseline. Of these, 6.0% developed type 2 diabetes during follow-up, the vast majority (95.5%) of whom had prediabetes at randomization, defined as (glycated hemoglobin (HbA1c) levels of 5.7–6.4% (39–46 mmol/mol).
Inzucchi reported that the rate of new-onset diabetes was 4.9% among the 1298 individuals who received dapagliflozin and 7.1% among the 1307 who received placebo, corresponding to a significant 32% reduction in risk with dapagliflozin.
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He said that this reduction “compares favorably with the 31% reduction with metformin, as reported in the Diabetes Prevention Program,” but that further studies are needed to determine how durable the benefit may be and whether it extends to patients without HFrEF.
The diabetes prevention effect of dapagliflozin was generally consistent across subgroups, but people aged 65 years and younger and those with an N-terminal pro b-type natriuretic peptide level at or below the median rather than above appeared to derive greatest benefit.
And the analysis also demonstrated that participants with versus without new-onset diabetes had a significantly higher mean baseline HbA1c (6.2 vs 5.7% [44 vs 39 mmol/mol]) and BMI (28.5 vs 27.1 kg/m2), and a significantly lower mean estimated glomerular filtration rate (61.5 vs 68.2 mL/min per 1.73 m2).
Finally, Inzucchi showed that individuals who developed diabetes during follow-up had a significant 70% increased risk for death from any cause and a significant 77% increased risk for cardiovascular death after adjusting for baseline features and treatment allocation.
He also noted that “[i]n contrast to other diabetes prevention trials with glucose-lowering medication, HbA1c was minimally reduced by dapagliflozin” in the DAPA-HF participants who were not diabetic at baseline.
“This may dispel concerns about merely ‘masking’ the development of diabetes, which has been raised with other diabetes prevention trials using glucose-lowering medications,” he remarked.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group
ADA Scientific Sessions; 12–16 June 2020
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