Four Pillars in Type 2 Diabetes and Chronic Kidney Disease G4-G5
Mission Impossible-or Not Too Late to Start?
This narrative review evaluates the evidence for four-pillar therapy (RAS inhibitors, SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists) in patients with type 2 diabetes and advanced chronic kidney disease (CKD G4-G5). While landmark trials largely enrolled patients with eGFR above 20–30 mL/min/1.73 m², pooled analyses and real-world data support a monitoring-based approach in CKD G4, whereas management in CKD G5 remains more individualized and extrapolative. Clinicians should actively identify missing pillars, avoid permanent discontinuation during acute events, and implement structured reinitiation to optimize cardiorenal outcomes.
Summary
The 4-pillar therapy-renin-angiotensin system inhibitors, sodium-glucose cotransporter 2 inhibitors, the nonsteroidal mineralocorticoid receptor antagonist finerenone, and glucagon-like peptide 1 receptor agonists-is increasingly applied to improve kidney and cardiovascular outcomes in adults with type 2 diabetes and chronic kidney disease (CKD). However, landmark trials underpinning current recommendations largely enrolled participants down to estimated glomerular filtration rate thresholds of ∼20-30 mL/min/1.73 m2, leaving uncertainty in CKD G4-G5. This uncertainty contributes to an implementation gap in advanced CKD, which is as follows: missing pillars are often not initiated, therapies are interrupted during clinical complications, and they are not reinitiated once acute triggers resolve despite high absolute kidney and cardiovascular risk. This narrative review summarizes what current evidence does-and does not-support for initiating, continuing, temporarily withholding, discontinuing, and reinitiating each pillar in type 2 diabetes and CKD G4-G5. We integrate posthoc and subgroup analyses of landmark trials, meta-analyses, and pooled analyses, including low-estimated glomerular filtration rate strata and observational real-world data. The main practical message is that current evidence generally supports a monitoring-based approach to 4-pillar therapy in CKD G4, whereas decisions in CKD G5 remain more individualized and explicitly extrapolative. For clinicians, the key priority is to identify missing pillars, avoid unnecessary permanent discontinuation, and use structured reinitiation when clinically appropriate.
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