GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Game Charger in the Field?

Abstract

Kidney disease is a public health epidemic affecting 10% of the population worldwide with a constantly rising incidence, and it is an important contributor to morbidity and mortality. Type 2 diabetes mellitus (T2DM) is a chronic complex condition with a rising incidence worldwide. T2DM remains the principal cause of chronic kidney disease (CKD), which is related to a high risk for cardiovascular (CV) events, end-stage kidney disease (ESKD), and, overall, considerable morbidity and mortality. In the past few decades, various therapeutic treatments have targeted the culprit pathways for slowing CKD progression, with partial success. Thus, despite new advances in patients' treatment, progressive loss of kidney function or death from T2DM and CKD complications compel new therapeutic pathways. Renin-angiotensin-aldosterone-system-blocking agents have been the only treatment until recently. On top of this, sodium-glucose co-transporter 2 inhibitors along with finerenone showed an impressive ability to reduce the progression of kidney disease and cardiovascular events in diabetic patients with CKD. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can play a special role and could be a game changer in this field. The latest FLOW trial confirmed multiple favorable clinical effects on renal, cardiovascular, and survival outcomes among high-risk patients treated with semaglutide and supports a significant therapeutic role for GLP-1RAs in this population, although larger-scale evaluation of their risks is needed, given their increasing use.

Keywords: GLP-1RA; chronic kidney disease; type 2 diabetes mellitus.

Figure 1

Renal effects of GLP-1RAs (proposed mechanisms). cAMP-PKA: cyclic adenosine monophosphate protein kinase A; eGFR: estimated glomerular filtration rate; LDL: low-density lipoprotein; NHE3: sodium–hydrogen exchanger 3; RAAS: renin–angiotensin–aldosterone system; ↓: reduced; ↑ increased.