Renal effects of sodium–glucose cotransporter-2 inhibitors in patients with type 2 diabetes and renal impairment

Abstract

In patients with type 2 diabetes (T2D), microvascular changes in the kidney often result in diabetic kidney disease (DKD), the progression of which is associated with an increased risk of cardiovascular (CV) and all-cause mortality. Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are a newer class of oral glucose-lowering therapies that were associated with significant reductions in the risk of major adverse CV events, CV death, and hospitalization for heart failure compared with placebo in CV outcomes trials (CVOTs) of patients with T2D and established CV disease or varying levels of CV risk. In addition, SGLT-2is reduced the risks of clinically relevant renal outcomes in these large randomized studies, indicating the potential for renoprotective effects in patients with T2D and DKD. This review discussed the non-glycemic effects of SGLT-2is in patients with T2D and renal impairment, including reductions in systolic and diastolic blood pressure, decreases in albuminuria and plasma uric acid, changes in estimated glomerular filtration rate, and minimal changes in electrolytes. Potential mechanisms for the renoprotective effects of SGLT-2is observed in CVOTs were considered, including the likely incremental benefits of SGLT-2is when added to renin-aldosterone-angiotensin system inhibitors (RAASis). The possibility of extending the use of SGLT-2is to patients with non-DKD was also discussed. Although the exact mechanisms by which SGLT-2is improve renal outcomes are not fully understood, they are likely to be multifactorial and additive when these drugs are used in combination with RAASis in patients with DKD.