Cardio-renal protection with empagliflozin

Cardiovascular (CV) and kidney disease are common and significant complications in people with type 2 diabetes (T2DM). CV disease is the leading cause of death, morbidly and hospitalisations for people with T2DM. Furthermore, diabetic kidney disease is a major risk factor for CV disease and is the main reason why patients need renal replacement therapy. In this perspective, we highlight the results of the recent landmark EMPA-REG OUTCOME trial which has shown that empagliflozin, a member of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor class of glucose lowering medications, reduces death from CV causes, hospitalisation for heart failure and progression to end stage kidney disease in patients with T2DM and established CV disease. The SGLT2 receptor mediates high-capacity glucose uptake in the early proximal tubule, and SGLT2 inhibitors, via their ability to promote glycosuria, have been developed as glucose lowering medications. As well as having a glucose lowering effect, SGLT-2 inhibitors also reduce blood pressure, promote weight loss and reduce uric acid levels. Potential side-effects or concerns related to the use of SGLT-2 inhibitors include increased rates of urinary tract infections, genital tract infections, postural hypotension, diabetic ketoacidosis, acute kidney injury and possible increased rates of fractures. The exact mechanisms that result in empagliflozin's dramatic CV and renal protective effects, with a very favourable safety/tolerability profile, in the EMPA-REG study remain to be fully defined. However, they are most likely distinct from the glucose lowering effects of empagliflozin. CV safety trials involving dapagliflozin and canagliflozin, members of the SGLT-2 class, are under way and the results from these studies will help to answer the question as to whether the cardio-renal benefits of empagliflozin are a class-effect or not. Without doubt, trials to investigate whether SGLT-2 inhibitors have cardio-renal protective effects in patients without diabetes will start soon.