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Dr John McMurray Explains the Heart Failure Benefits of Dapagliflozin in Patients With and Without Diabetes

In patients with heart failure, both with and without diabetes, dapagliflozin was shown to provide identical efficacy and possibly beneficial effects on the heart, said John McMurray, MD, FRCP, FESC, professor of medical cardiology in the Institute of Cardiovascular and Medical Sciences at the University of Glasgow.


In patients with heart failure, both with and without diabetes, dapagliflozin was shown to provide identical efficacy and possibly beneficial effects on the heart, said John McMurray, MD, FRCP, FESC, professor of medical cardiology in the Institute of Cardiovascular and Medical Sciences at the University of Glasgow.

Transcript

Why would the heart failure benefits of dapagliflozin be nearly identical for patients with and without diabetes?

The benefits of dapagliflozin were identical in patients with and without diabetes, and even more so, among the patients without diabetes, the benefits of dapagliflozin were consistent right across the spectrum of glycated hemoglobin. So, even patients with a completely normal hemoglobin A1C got as much benefit as other patients. Clearly, that questions the idea that in heart failure, this is just about lowering glucose. In fact, the patients without diabetes, randomized to dapagliflozin, had no reduction in hemoglobin A1C either–again, questioning the benefits in heart failure just being about reducing glucose. So, the alternative possibilities are that these agents do have, at least in the short term, a diuretic effect–that might be beneficial, but it's unlikely to be the whole explanation.

These drugs do protect the kidneys, slow the progressive deterioration of renal function that we see in patients with heart failure, and we've reported that with dapagliflozin, both in patients with and without diabetes. Then I think the third idea, at least, is that these drugs might have beneficial effects on the heart. Now, these are largely still in human beings’ hypotheses, but probably the 2 major ones are, firstly, that these drugs might improve myocardial energetics, make the heart more metabolically efficient, and then that way work better. One reason why that might be is because they increase the production of ketones. You can think of ketones, the very simplistic way, as a super fuel for the heart that are more metabolically efficient. Then the other explanation, but again, very hypothetical and experimental, is that SGLT2 inhibitors might interact with what's called the sodium hydrogen exchanger on heart muscle cells, cardiomyocytes. By reducing intracellular sodium, might, for example, reduce the risk of sudden death; but we don't have any firm human evidence for that–it's a speculative mechanism.

 
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