SGLT2 Inhibitors: A New Therapeutical Strategy to Improve Clinical Outcomes in Patients with Chronic Kidney Diseases

Abstract

The purpose of this manuscript is to review the effects of sodium-glucose cotransport protein 2 inhibitors (SGLT2is) in patients with chronic kidney disease according to basic mechanisms, current recommendations, and future perspectives. Based on growing evidence from randomized, controlled trials, SGLT2is have proven their benefit on cardiac and renal adverse complications, and their indications expanded into the following five categories: glycemic control, reduction in atherosclerotic cardiovascular disease (ASCVD), heart failure, diabetic kidney disease, and nondiabetic kidney disease. Although kidney disease accelerates the progression of atherosclerosis, myocardial disease, and heart failure, so far, no specific drugs were available to protect renal function. Recently, two randomized trials, the DAPA-CKD and EMPA-Kidney, demonstrated the clinical benefit of the SGLT2is dapagliflozin and empagliflozin in improving the outcome in patients with chronic kidney disease. For the consistently positive results in cardiorenal protection, the SGLT2i represents an effective treatment to reduce the progression of kidney disease or death from cardiovascular causes in patients with and without diabetes mellitus.

Keywords: SGLT2 inhibitors; cardiovascular disease; chronic kidney disease; heart failure; type 2 diabetes mellitus.

Figure 1

The figure is designed on data from the EMPA−REG−OUTCOME, CREDENCE, and DAPA−CKD studies. The figure shows the typical changes in eGFR caused by the use of SGLT2 inhibitors. In the first month, the eGFR dip is about 5 mL/min/1.73 m² but returns towards initial values in 6 months. Thereafter the eGFR decline is slower than in subjects treated with a placebo.

Figure 2

Cardiorenal protection of SGLT2i. SGLT2i have a beneficial effect: these drugs reduced chronic kidney disease progression and increased cardiac function, regardless of the presence or absence of T2DM. HIF-2α, Hypoxia-inducible factor 2α; FFA, free fatty acid; HF, heart failure.