Research enhances understanding of how diabetes drug reduces cardiac risks

Researchers at the University of Dundee have enhanced the understanding of how a new class of anti-diabetes drugs appears to improve the outcome for patients with heart failure.

In two papers presented at the European Society of Cardiology conference, academics from the University’s School of Medicine provided new insights into the potential cardiovascular benefits of sodium glucose linked cotransporter 2 (SGLT2) inhibitors.

These drugs, originally developed for the treatment of diabetes, have recently been shown to reduce the number of hospitalisations as a result of heart failure, a condition caused by the heart not pumping efficiently.

Diabetes and heart disease frequently present together and can prove to be a potentially lethal combination. SGLT2 inhibitors act to lower blood sugar via the kidneys while also increasing urinary volume, lowering blood pressure and inducing weight loss, all of which have potentially beneficial cardiovascular effects.

Results from two clinical trials examining the effects of SGLT2 inhibitors on the cardiovascular system were presented at the ESC conference.

In the first of these, an SGLT2 inhibitor called dapagliflozin was shown to improve the pumping function of the heart.

“Following a year of treatment with dapagliflozin at a dose of 10mg daily, there was a significant improvement in function measured in an echocardiogram, a scan of the heart,” said Dr Alex Brown, who carried out the research. “This is important as it provides evidence that SGLT2 inhibitors can cause positive effects on the pumping function of the heart.”

Dr Brown’s presentation was accompanied by simultaneous publications in the Journal of the American College of Cardiology Cardiovascular Imaging. The research was funded by AstraZeneca.

Researchers working on the other trial attempted to gauge the effects of an SGLT2 called empagliflozin on the heart and kidneys in diabetic patients.

“People with heart failure are prone to retaining fluid, causing leg swelling and fluid on the lungs, and doctors often try to prevent this by prescribing patients water tablets,” said Dr Natalie Mordi. Patients can require large doses of water tablets which can cause a loss of sodium from their bodies, upsetting the balance of salts in the blood.

“We found that in patients with type 2 diabetes and heart failure, there was a quick, large and sustained increase in urine volume when they took empagliflozin in combination with their traditional water tablets. Importantly, we also found that although empagliflozin improved fluid loss, participants did not lose any more sodium. Additionally the participants studied saw other beneficial effects such as significant weight loss and a reduced water tablet requirement.

“These findings help us understand empagliflozin’s diuretic effect. More and more patients are likely to be prescribed empagliflozin in the future, and these results should give doctors and patients more understanding on how this tablet works.”

This research was funded by the British Heart Foundation and has been published in Circulation.

Further work at the University led by Professor Chim Lang and Dr Ify Mordi is exploring the strategy of repurposing diabetic therapies for cardiovascular treatment.