medwireNews: The use of the sodium glucose cotransporter (SGLT) 2 inhibitor dapagliflozin is associated with a reduced risk of developing type 2 diabetes in high-risk people with heart failure and reduced ejection fraction (HFrEF), suggesting an exploratory analysis of the data from the DAPA-HF study.
This is “the first study to suggest a diabetes-preventing effect of an SGLT2 inhibitor,” say Silvio Inzucchi (Medical School of Yale University, New Haven, Connecticut, USA) and co-investigators.
Overall, 4.9% of 1298 people without pre-existing diabetes who were treated with 10 mg dapagliflozin / day developed an incident of diabetes during a mean follow-up of 18.2 months, compared with 7.1% of 1307 in the placebo group . These results led to incidence rates of 3.4 and 5.0 per 100 person-years and a significant hazard rate of 0.68 in favor of dapagliflozin.
“Interestingly, this effect size is almost identical to that in the [Diabetes Prevention Program] with metformin, the drug most commonly considered for diabetes prevention, ”the researchers note.
They also note that a difference between the groups in diabetes incidence rates was identified early and “can be seen by the 4-month visit”.
Risk reduction was “primarily driven by baseline prediabetes subjects,” say Inzucchi et al. In fact, 95.5% of the 157 people from both groups who got diabetes had prediabetes according to the ADA definition of glycated hemoglobin (HbA1c) between 5.7% and 6.4% (39-46 mmol / mol) while 86.6% had prediabetes at HbA1c levels of 6.0–6.4% (42–46 mmol / mol) according to the criteria of the International Expert Committee.
The team also found that people who developed diabetes had a 1.7 times higher risk of mortality than people who did not develop diabetes after adjusting baseline factors and treatment assignment, with a rate of 16.6 versus 7.2 per 100 person-years. They say, that “[s]Similar results were observed for death from cardiovascular causes. “
DAPA-HF is “the first study to show that a single drug can prevent both diabetes and death, albeit in a specific group of patients with heart failure,” write researchers in Diabetes Care.
They indicate that these benefits occurred “with no significant impact on mean HbA1c”. The mean HbA1c levels at the start of the study were 5.7% (39 mmol / mol) and 5.8% (40 mmol / mol) in the dapagliflozin and placebo groups and remained constant in both groups at the 8-month follow-up examination at 5.8%.
These data “could provide further insight into the underlying effect of SGLT2 inhibition on the dysfunction of β-cells in the progression from prediabetes to diabetes – a term that warrants further mechanistic investigation,” said Inzucchi and his team.
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Diabetes Care 2021; 44: 586-594
