Preventing T2D: another string to the SGLT2i bow?

Professor Silvio Inzucchi

Dapagliflozin is the first SGLT2 inhibitor shown to prevent type 2 diabetes in patients with heart failure and a reduced ejection fraction (HFrEF), according to a presentation at the ADA 2020 virtual scientific sessions .

Endocrinologist Professor Silvio Inzucchi, from Yale School of Medicine, presented the latest update from the DAPA-HF study. The trial randomised HFrEF patients with and without diabetes to 10 mg dapagliflozin daily or placebo, and has recently reported a lower risk of worsening heart failure or deaths from cardiovascular causes with the SGLT2 inhibitor compared to controls.

There was a similar benefit from dapagliflozin regardless of the presence or absence of diabetes at baseline.

In the latest study, 2,605 of the patients who did not have diabetes at baseline were followed for the development of diabetes. About a third were normoglycaemic and two-thirds had prediabetes.

“Amongst more than 2,500 trial participants without diabetes at baseline, 157 or 6.0% developed type 2 diabetes during the trial,” he said.

The incidence of new onset diabetes was 4.9% in patients receiving dapagliflozin compared to 7.1% of controls after a follow-up of 18.2 months (HR 0.68; p=0.019).

Professor Inzucchi said although the study was not a traditional diabetes prevention trial, the 32% risk reduction in type 2 diabetes was promising.

“While the major role of dapagliflozin in patients with HFrEF is to reduce CV mortality and worsening of HF, decreasing the incidence of diabetes may be considered an additional benefit especially since incident type 1 diabetes is associated with greater mortality.”

Baseline factors predicting types 2 diabetes were a higher BMI (28.5 v 27.1) and a higher HbA1c (6.2% v 5.7%).

He added there was a stronger effect from dapagliflozin in younger patients and those with a lower NT-proBNP.

Australian perspective

Professor Jerry Greenfield, head of diabetes and endocrinology at St Vincent’s Hospital in Sydney, told the limbic the findings would appear to increase the potential breadth of use of the SGLT2 inhibitors in the future.

However the findings would have to be replicated in other studies that were specifically designed to look at the question of diabetes prevention, he said.

“Whilst the findings cannot be extrapolated beyond individuals with baseline HFrEF, the study reinforces the importance of dapagliflozin as both a therapeutic agent for the treatment of type 2 diabetes and, possibly, an additional agent to prevent the onset of type 2 diabetes in patients with heart failure.”

Professor Greenfield said while the SGLT2 inhibitors were preferentially recommended for patients with type 2 diabetes and heart failure – by improving glycaemic control and reducing the risk of admission for heart failure – they are not currently approved for people without diabetes, despite growing evidence.

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