Diabetic kidney disease remains a leading cause of end-stage kidney disease, but its management has been reorganized around four complementary "pillars," each with strong trial support, and the frontier is now combining them.
The four pillars
RAAS blockade (ACE inhibitors or ARBs) remains foundational for albuminuria and progression. SGLT2 inhibitors slow CKD progression and reduce heart-failure and mortality risk across diabetic and non-diabetic kidney disease, and are now standard add-ons. Finerenone, a non-steroidal mineralocorticoid receptor antagonist, reduced kidney and cardiovascular events in FIDELIO-DKD and the pooled FIDELITY analysis, with hyperkalemia the main risk. The newest pillar is the GLP-1 receptor agonist semaglutide, which in the FLOW trial reduced major kidney events by 24%, slowed eGFR decline, and lowered cardiovascular events and all-cause mortality — benefits seen regardless of background SGLT2-inhibitor use.
Combining the pillars
The key 2025 development is a shift from sequential to combination therapy. The CONFIDENCE trial tested simultaneous initiation of finerenone plus an SGLT2 inhibitor against either agent alone, finding that the combination produced a greater reduction in albuminuria — supporting earlier, layered use of these mechanisms rather than adding them one at a time. Endothelin antagonists and other agents are also under study as further add-ons.
| Therapy | Key outcome | Magnitude |
|---|---|---|
| Semaglutide (FLOW) | Kidney failure, CV events, death | ~24% reduction in major kidney events |
| Finerenone (FIDELIO/FIDELITY) | Kidney and CV events | ~18% renal, ~14% CV |
| SGLT2 inhibitors | Kidney, CV, mortality | ~30–40% relative risk reduction (class) |
| Finerenone + SGLT2 (CONFIDENCE) | Albuminuria | Greater reduction than either alone |
Further reading: FLOW semaglutide (Perkovic et al., NEJM 2024); FIDELIO-DKD finerenone (Bakris et al., NEJM 2020) and FIDELITY pooled analysis; CONFIDENCE combination trial (2025); SGLT2-inhibitor CKD trials (DAPA-CKD, EMPA-KIDNEY).