Evolving strategies for nephroprotection in diabetic kidney disease: From established therapies to novel interventions

Table 1 Stepwise pharmacological approach to nephroprotection in diabetic kidney disease

Risk/disease stage	Therapeutic focus	Pharmacological choice	Expected nephroprotective effect
Diabetes with preserved estimated GFR, no albuminuria	Early risk reduction	Metformin	Slows early kidney function decline
DKD with confirmed albuminuria	Hemodynamic and albuminuria control	ACEi or ARB	Reduces albuminuria and rate of estimated GFR loss
DKD at any stage with albuminuria	Kidney-protective core therapy	SGLT2i	Slows progression of kidney disease and reduces risk of kidney failure
Persistent albuminuria despite core therapy	Residual renal risk reduction	Finerenone	Further attenuates DKD progression
DKD with metabolic and cardiovascular risk	Metabolic-renal risk modulation	GLP-1 receptor agonist	Lowers albuminuria and slows kidney function decline
Advanced DKD with persistent albuminuria despite monotherapy	Comprehensive multi-target nephroprotection	SGLT2i + Finerenone ± RAS blockade	Additive reduction in kidney failure risk through complementary mechanisms
When preferred agents are not tolerated	Alternative glucose-lowering strategy	DPP-4 inhibitor	Renally safe glucose-lowering option
Marked albuminuria, evolving strategies	Enhanced albuminuria control	Tirzepatide	Dose-dependent reduction in albuminuria

ACEi: Angiotensin-converting enzyme inhibition; ARB: Angiotensin receptor blocker; DKD: Diabetic kidney disease; GFR: Glomerular filtration rate; GLP-1 RA: Glucagon-like peptide-1 receptor agonist; RAS: Renin-angiotensin system; SGLT2i: Sodium-glucose co-transporter 2 inhibitor; DPP-4: Dipeptidyl peptidase-4.