SGLT2 inhibitors: Emerging roles in the protection against cardiovascular and kidney disease among diabetic patients

Purpose of Review: Type 2 diabetes mellitus (T2DM) is a prevalent disease with the severe clinical implications including myocardial infarction, stroke, and kidney disease. Therapies focusing on glycemic control in T2DM such as biguanides, sulfonylureas, thiazo-lidinediones, and insulin-based regimens have largely failed to substantially improve cardiovascular and kidney outcomes. We review the recent findings on sodium-glucose cotransporter type 2 (SGLT2) inhibitors which have shown to have beneficial cardiovascular and kidney-related effects. Recent Findings: SGLT2 inhibitors are a new class of diabetic medications that reduce the absorption of glucose in the kidney, decrease proteinuria, control blood pressure, and are associated with weight loss. SGLT2 inhibitors provide complementary therapy independent of insulin secretion or action with proved glucose-lowering effects. Recent placebo-controlled clinical trials have demonstrated that these medications can decrease cardiovascular death, progression of kidney disease, and all-cause mortality in diabetic and non-diabetic patients. Interestingly, SGT2 inhibitors such as dapagliflozin have also proven to decrease heart failure admissions and cardiovascular endpoints in non-diabetic patients, suggesting pleiotropic effects. The exact mechanisms responsible for reductions in atherosclerotic heart disease, need for kidney replacement therapy, and progressive kidney disease remain unknown. While regulation of glomerular hyperfiltration, albuminuria, and natriuresis may be part of the explanation, it is possible that complex cellular effects including energy balance optimization, downregulation of oxidative stress, and modulation of pro-inflammatory signaling pathways are associated with favorable outcomes observed in large clinical studies. Conclusion: SGLT2 inhibitors are novel antidiabetic medications with immense utility in the management of patients with T2DM. Furthermore, SGLT2 inhibitors have demonstrated to reduce the progression to advanced forms of kidney disease and its associated complications. These medications should be front and center in the management of patients with diabetic kidney disease with and without chronic kidney disease as they confer protection against cardiovascular/renal death and improve all-cause mortality. Future studies should evaluate the benefits and implications of early initiation of SGLT2 inhibitors, as well as the long-term effects of this therapy.