Uric acid and the cardio-renal effects of SGLT2 inhibitors

Abstract

Sodium/glucose co‐transporter‐2 (SGLT2) inhibitors, which lower blood glucose by increasing renal glucose elimination have been shown to reduce the risk of adverse cardiovascular (CV) and renal events in type 2 diabetes. This has been ascribed in part to haemodynamic changes, body weight reduction and several possible effects on myocardial, endothelial and tubulo‐glomerular functions as well as reduced glucotoxicity. This review evaluates evidence that an effect of SGLT2 inhibitors to lower uric acid may also contribute to reduced cardio‐renal risk. Chronically raised circulating uric acid concentrations are associated with increased risk of hypertension, CV disease and chronic kidney disease (CKD). The extent to which uric acid contributes to these conditions either as a cause or aggravating factor remains unclear, but interventions that reduce urate production or increase urate excretion in hyperuricaemic patients have consistently improved cardio‐renal prognoses. Uric acid concentrations are often raised in type 2 diabetes, contributing to the ‘metabolic syndrome’ of CV risk. Treating type 2 diabetes with an SGLT2 inhibitor increases uric acid excretion, reduces circulating uric acid and improves parameters of CV and renal function. This raises the possibility that the lowering of uric acid by SGLT2 inhibition may assist in reducing adverse CV events and slowing progression of CKD in type 2 diabetes. SGLT2 inhibition might also be useful in the treatment of gout and gouty arthritis, especially when co‐existent with diabetes.