Expert perspectives on incorporating glucagon-like peptide-1 receptor agonist in diabetes and chronic kidney disease: challenges and opportunities

Chronic kidney disease (CKD) is a complex and progressive condition ultimately leading to premature death. Diabetes is the leading cause of end-stage kidney disease worldwide. Up till 2024, international clinical guidelines have established three therapeutic pillars to delay CKD progression in people with type 2 diabetes (T2D): renin-angiotensin system inhibitors, sodium-glucose cotransporter 2 inhibitors, and the non-steroidal mineralocorticoid receptor antagonist finerenone. With the recent results from the Evaluate Renal Function with Semaglutide Once Weekly study, the glucagon-like peptide-l receptor agonist (GLP-1 RA) class is now considered a new therapeutic pillar in reducing CKD complications in this patient population. In this expert opinion, we identify patient populations at risk of developing new onset or worsening pre-existing CKD to explore optimal therapeutic strategies, introducing GLP-1 RAs. We highlight the important challenges that remain in optimising, sequencing, and combining these four therapeutic pillars. Even though the conventional approach of combining the pillars has been based on the historical emergence of evidence, we discuss the factors that would influence physicians' decision for preferring one pillar over another, and for selecting a certain combination, whether performed simultaneously or sequentially. These factors include the grade of CKD and the level of albuminuria; diabetic control (glycaemia); comorbidities: atherosclerotic cardiovascular disease, heart failure, obesity; concomitant medications; biological variables: potassium serum levels. The efficacy and safety profiles of each pillar, as demonstrated in landmark trials that have clearly shown the nephroprotective effects, along with real-world data, should also be carefully considered when selecting the most appropriate therapeutic option.