A recently published study by scientists from King’s College London, University of Oxford, University of Glasgow and University of Birmingham sheds light on the mechanism of action of an exciting new class of drugs recently discovered to be effective treatments for heart failure - the SGLT2 inhibitors.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been widely used to treat diabetes. Diabetologists quickly observed that their patients who also suffered from heart failure got better independent of whether their diabetes improved. However, since the target of these drugs is not present in the heart, the mechanism through which these drugs works is unknown.

It was thought that these drugs act on a cardiac protein called the Na/H exchanger. In this study funded by the British Heart Foundation, a team of scientists comprehensively showed that SGLT2 inhibitors do not work via a previously proposed mechanism. By using state-of-the-art technology, research team led by Professor Michael Shattock showed that SGLT2 inhibitors do not affect the sodium hydrogen exchanger in the heart and thereby do not modulate intracellular sodium levels. This study significantly alters our understanding of the manner in which these drugs work and allows the scientific community to focus on discovering the real mechanism by which these drugs benefit the patients with heart failure.

Dr Davor Pavlovic, a senior lecturer at the Institute of Cardiovascular Sciences (ICVS), University of Birmingham and a co-author on the study stated: “It is essential that we understand why SGLT2 inhibitors benefit heart failure patients. I am pleased that our work helps clarify some of the misconceptions about the mode of action of this exciting new drug class.”

Dr Yujin Chung, first author on this study, said: “Science is not always about finding out what things do.  Sometimes, it is equally important to find out what they don’t do!” 

Professor Shattock added: We urgently need better therapies to treat heart failure. Understanding how this exciting class of drugs work in the heart is therefore really important. A better understanding of their mechanism may allow us to develop better therapies for this debilitating and deadly disease.”