Dapagliflozin may reduce diabetes risk in people with heart failure
medwireNews: Use of the sodium-glucose cotransporter (SGLT)2 inhibitor dapagliflozin is associated with a reduced risk for new-onset type 2 diabetes in high-risk individuals with heart failure and reduced ejection fraction (HFrEF), suggests an exploratory analysis of data from the DAPA-HF trial.
This is “the first study to suggest a diabetes prevention effect from an SGLT2 inhibitor,” say Silvio Inzucchi (Yale University School of Medicine, New Haven, Connecticut, USA) and co-investigators.
In all, 4.9% of 1298 people without pre-existing diabetes who were treated with dapagliflozin 10 mg/day developed incident diabetes during a median follow-up of 18.2 months, compared with 7.1% of 1307 in the placebo group. These findings translated into incidence rates of 3.4 and 5.0 per 100 person–years, respectively, and a significant hazard ratio of 0.68 favoring dapagliflozin.
“Interestingly, this effect size is nearly identical to that demonstrated in the [Diabetes Prevention Program] with metformin, the drug most commonly considered for use in diabetes prevention,” remark the researchers.
They also note that a between-group difference in diabetes incidence rates was seen early, and “detectable by the 4-month visit.”
The risk reduction was “predominantly driven by individuals with prediabetes at baseline,” say Inzucchi et al. Indeed, of the 157 people from both groups who developed diabetes, 95.5% had prediabetes according to the ADA definition of glycated hemoglobin (HbA1c) levels between 5.7% and 6.4% (39–46 mmol/mol), while 86.6% had prediabetes based on HbA1c levels of 6.0–6.4% (42–46 mmol/mol) as per International Expert Committee criteria.
The team also found that people who developed incident diabetes had a 1.7-fold higher mortality risk than those who did not develop diabetes after adjustment for baseline factors and treatment assignment, at rates of 16.6 versus 7.2 per 100 person–years. They say that “[s]imilar results were observed for death from cardiovascular causes.”
DAPA-HF is “the first study to demonstrate that a single drug may prevent both diabetes and death, albeit in a specific group of patients with heart failure,” write the investigators in Diabetes Care.
They point out that these benefits occurred “without a significant effect on mean HbA1c.” Average HbA1c levels at baseline were 5.7% (39 mmol/mol) and 5.8% (40 mmol/mol) in the dapagliflozin and placebo groups, respectively, remaining consistent at 5.8% in both groups at the 8-month follow-up.
These data “may provide further insights into the underlying effect of SGLT2 inhibition on β-cell dysfunction in the progression from prediabetes to diabetes – a notion that will require further study of a more mechanistic nature,” say Inzucchi and team.
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