New Era for Renal-Protective Therapy in Type 2 Diabetes: Better Renal Outcomes in Patients with Type 2 Diabetes Taking Sodium-Glucose Cotransporter 2 Inhibitors versus Dipeptidyl Peptidase-4 Inhibitors.

Abstract

Diabetes is the most common cause of chronic kidney disease (CKD) globally. Diabetes and CKD commonly coexist and are associated with a high risk for cardiovascular (CV) morbidity and mortality. Diabetic kidney disease (DKD) is very prevalent, and the proportion of Korean adults >30 years of age with diabetes who had either albuminuria or CKD was found to be over 30% [1]. The global burden of DKD or DM-induced end-stage renal disease (ESRD) has continued unabated even though allcause mortality and CV mortality are generally declining. Until recently, the only treatment with a demonstrated ability to attenuate DKD was a renin-angiotensin system (RAS) blocker. In addition, residual nephropathy risk remained present in patients with type 2 diabetes mellitus (T2DM) despite multifactorial intensive medical therapy, including antihypertensive agents such as RAS blockers [2]. A progressive decline in renal function in CKD patients has been regarded as an inevitable and unstoppable fact. Just a few years ago, no class of glucose-lowering agent was considered to be the preferred treatment. Instead, all glucoselowering medication has been considered equal, with a focus on glucose control rather than end-organ protection and comorbidities. More than 22 randomized controlled trials (RCTs) of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide receptor agonists (GLP-1RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors on CV or kidney outcomes have been completed, resulting in tremendous evidence that has led to major changes in diabetes care in just 10 years [3]. From several CV trials and dedicated kidney outcome trials, SGLT2 inhibitors have already achieved stardom due to their ability to slow the rate of CKD progression and improve renal outcomes in T2DM. Major endocrinology, nephrology, and cardiology clinical practice guidelines are rapidly updating their recommendations to reflect the emerging evidence that SGLT2 inhibitors provide benefits in terms of CV and kidney protection [4-7]. All current guidelines recommend SGLT2 inhibitors for patients with T2DM who have atherosclerotic cardiovascular disease (ASCVD), CKD, and heart failure (HF). In addition, the European Society of Cardiology and the European Association for the Study of Diabetes guidelines recommend SGLT2 inhibitors independent of metformin [5]. SGLT2 inhibitors are even beginning to be used as the first-line therapy in patients with T2DM who have ASCVD, HF, or CKD. Three important RCTs assessed the protective effect of DPP4 inhibitors on renal function. The Saxagliptin Assessment of