Emerging therapies for diabetic kidney disease: beyond SGLT2 inhibitors

Diabetic kidney disease (DKD) remains the leading cause of kidney failure and death worldwide despite established therapies targeting the renin-angiotensin system and, more recently, sodium glucose cotransporter-2 inhibitors. Although contemporary guideline-directed therapy has substantially improved kidney and cardiovascular outcomes, significant residual risk of disease progression persists. This unmet need has driven the development of a new generation of therapies targeting complementary metabolic, inflammatory, fibrotic, and hemodynamic pathways implicated in DKD pathogenesis.

This review summarizes contemporary guideline-directed therapy for DKD and examines emerging therapeutic strategies targeting complementary pathways implicated in kidney disease progression. These include novel incretin-based therapies, aldosterone synthase inhibitors, endothelin receptor antagonists, soluble guanylate cyclase activators, and therapies directed against inflammatory and fibrotic mediators. We also discuss the growing role of combination therapy, implementation challenges, and future precision medicine approaches aimed at further reducing residual cardiorenal risk.

Advances in the management of DKD support a paradigm shift from sequential escalation to early combination therapy aimed at maximizing cardiorenal protection and will require novel care models. Significant gaps remain in extending cardiorenal protective therapies to understudied high-risk groups, including type 1 diabetes. Further research should also focus on real-world outcomes beyond albuminuria reduction and target kidney disease remission.