SGLT2 inhibitors in patients with type 2 diabetes and renal disease: overview of current evidence
Chronic kidney disease (CKD) is a frequent complication of type 2 diabetes mellitus (T2DM) and is associated with poor clinical outcomes, including an increased risk of all-cause and cardiovascular mortality, as well as adverse economic and social effects. Slowing the development and progression of CKD remains an unmet clinical need in patients with T2DM. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are widely used for the management of T2DM and have effects beyond glucose lowering that include cardiovascular benefits and potential renoprotective effects. Although the glucose-lowering efficacy of these agents is dependent on renal function, the cardiovascular and renal benefits of SGLT2 inhibition appear to be maintained to estimated glomerular filtration levels as low as 30 mL/min/1.73 m2. Clinical evidence has indicated that these agents can reduce the risk of development or worsening of albuminuria, a marker of renal damage, through a range of mechanisms. These include blood pressure lowering, reduction of intraglomerular pressure and hyperfiltration, modification of inflammatory processes, reduction of ischemia-related renal injury, and increases in glucagon levels. The blood pressure-lowering effect of SGLT2 inhibitors is maintained in people with CKD and could further contribute to reduced renal burden, as well as potentially offering synergistic effects with antihypertensive therapies in these patients. Several cardiovascular outcomes trials (CVOTs) have included renal endpoints, adding to the growing evidence of the potential renoprotective effects of these agents in patients with T2DM. Several ongoing dedicated renal outcomes trials will provide further guidance on the potential clinical role of SGLT2 inhibitors in slowing the development and progression of renal impairment in individuals with T2DM.