Beyond current standards: combination therapy and emerging targets in diabetic kidney disease

Diabetic kidney disease continues to be a major contributor to kidney failure and is strongly associated with adverse cardiovascular outcomes. Even with routine use of renin-angiotensin system blockade, many patients show ongoing disease progression, indicating that current treatment alone is often insufficient. Treatment approaches are increasingly focused on combining agents that act through different biological pathways. Among these, sodium-glucose cotransporter 2 inhibitors have taken a central role, supported by consistent evidence for kidney and cardiovascular protection. Their use alongside nonsteroidal mineralocorticoid receptor antagonists, particularly finerenone, has further strengthened this strategy. Glucagon-like peptide-1 receptor agonists are also being incorporated into clinical practice, largely because of their metabolic and vascular effects, although direct evidence for additional kidney benefit remains limited. Interest has also grown in therapies that target pathways not fully addressed by existing drugs. Aldosterone synthase inhibitors reduce aldosterone production at its source, whereas endothelin receptor antagonists act on mechanisms linked to persistent albuminuria and progressive fibrosis. These approaches may help address residual risk in diabetic kidney disease, particularly in patients with persistent albuminuria despite optimized therapy. Data supporting multidrug or triple therapy remain limited. Nonetheless, current evidence suggests that earlier use of combination therapy may offer advantages. Further research is needed to determine how best to integrate these treatments and to confirm their long-term effects on kidney and cardiovascular outcomes.