Romanian Society of Pharmaceutical Sciences
 

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A PARADIGM SHIFT FOR THE SGLT2 INHIBITORS – TREATING THE HEART WITH ANTI-HYPERGLYCAEMIC DRUGS

ELISABETA BĂDILĂ 1,2, ANA-MARIA BALAHURA 1,2*, MARILENA STOIAN 1,3, DANIELA
BARTOȘ 1,2, DRAGOȘ VINEREANU 1,4

1Department of Internal Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021,
Bucharest, Romania
2Department of Internal Medicine, Clinical Emergency Hospital Bucharest, 8 Floreasca Street, 014461, Bucharest, Romania
3Department of Internal Medicine, “Dr. I. Cantacuzino” Clinical Hospital, 5-7 Ion Movilă Street, 030167, Bucharest, Romania
4Department of Cardiology, University and Emergency Hospital, 169 Splaiul Independenței, 050098, Bucharest, Romania

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Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a newer class of anti-hyperglycaemic drugs that act by partially inhibiting glucose reabsorption from the renal filtrate and inducing glycosuria. However, they have several other benefits, independent of the glycaemic control. SGLT2i reduced major cardiovascular events, including new-onset heart failure, in patients with type 2 diabetes mellitus (T2DM), in large randomized clinical trials. These effects have been recently described in patients with HF with reduced ejection fraction, irrespective of their diabetic or glycated haemoglobin status, suggesting that their benefits are driven independently of their glucose lowering properties. This review summarizes the current evidence for their cardioprotective effects, and provides an overview of the possible mechanisms for the cardiovascular benefits. The alleged mechanisms that lead to improve cardiovascular outcome, even though still incompletely understood, include an association between improvement in cardiac pre- and after-load, partially explained by osmotic diuresis and natriuresis, prevention of cardiac remodelling, direct cardiac effects with improved cardiac energetics and ion handling, antiinflammatory effects, and anti-fibrotic effects. Therefore, in the latest years, both mechanistic insights, as well as major trials data, have repurposed SGLT2i usage from only anti-diabetic to potent HF treatment drugs, and new indications have been attributed to these compounds in HF guidelines.