Glucagon-like Peptide Receptor Agonists (GLP-1 receptor agonists): A Powerful Addition to Foundational Therapy Kidney Care in Patients with Type 2 Diabetes Mellitus

Abstract

There has been a veritable explosion in therapeutic options for patients with chronic kidney disease (CKD) and Type 2 diabetes mellitus (T2DM). For the past several decades, therapy for this condition has been limited to glycemic control, blood pressure control and utilization of angiotensin converting enzyme inhibitors (ACEi’s) or angiotensin 2 receptor blockers (ARBs). Recently, the emergence of therapies with organ protective effects has completely altered the landscape of therapy and outcomes for CKD in T2DM. Specifically, several large randomized clinical trials have demonstrated the positive impact of sodium glucose luminal transporter 2(SGLT2) inhibitors on the progression of kidney disease, end-stage kidney disease (ESKD), major adverse cardiovascular events (MACE), cardiovascular (CV) death, hospitalization for heart failure(HHF), all‑cause hospitalization, and all-cause mortality. Furthermore, finerenone, a non-steroidal mineralocorticoid receptor (nsMRA), has also been established as a component of foundational kidney therapy in patients with T2DM. A robust clinical trial program demonstrated kidney protection, CV protection and reductions in HHF in patients with CKD and T2DM. International guidelines have been updated to incorporate these agents as standards of care in this group of patients. CKD in T2DM is a complex disease and it stands to reason that multi‑targeted therapy could result in better outcomes for patients, similar to the management of patients with chronic heart failure. Those who follow this field will have noted that GLP-1 receptor agonists are listed as a component of guideline-directed management. However, these recommendations are based on the CV protective effect of these agents. Until recently, it was not clear if GLP‑1RA’s possessed kidney protective properties. The recent publication of the FLOW trial confirms that GLP-1 receptor agonists are, in fact, kidney protective.