Cardiorenal Protection in Diabetic Kidney Disease

Abstract

Over the last 5 years there have been many new developments in the management of diabetic kidney disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT2) inhibitors were initially used for glycemic control, but more recent studies have now shown that their benefits extend to cardiovascular and kidney outcomes. The recent addition of data on the novel mineralocorticoid receptor antagonist (MRA) gives us another approach to further decrease the residual risk of diabetic kidney disease progression. In this review we describe the mechanism of action, key studies, and possible adverse effects related to these three classes of medications. The management of type 2 diabetes now includes an increasing number of medications for the management of comorbidities in a patient population at significant risk of cardiovascular disease and progression of chronic kidney disease. It is from this perspective that we seek to outline the rationale for the sequential and/or combined use of SGLT2 inhibitors, GLP-1 RA and MRAs in patients with type 2 diabetes for heart and kidney protection.

Keywords: Cardiovascular diseases; Diabetes mellitus, type 2; Diabetic nephropathies; Glucagon-like peptide-1 receptor; Heart failure; Mineralocorticoid receptor antagonists; Sodium-glucose transporter 2 inhibitors.

Fig. 1

Decision algorithm for prescribing sodium-glucose cotransporter-2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonist (GLP-1 RA) and mineralocorticoid receptor antagonist (MRA) to optimize heart and kidney protection in patients with diabetic kidney disease. ACEi, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; UACR, urinary albumin-to-creatinine ratio; HF, heart failure; ASCVD, atherosclerotic cardiovascular disease. ^aEMPA KIDNEY trial may allow use of SGLT2i down to eGFR of 20 without albuminuria; ^bFIGARO trial in progress which will give further information on use of MRA in HF and ASCVD; ^cAdd on if residual albuminuria with UACR >30 mg/g despite optimal medical therapy; ^dFLOW trial may suggest GLP-1 RA use to prevent composite renal outcome; ^eMetabolic risk, poor glycemic control or weight loss desired.