The last decade has transformed CKD management through five landmark trials. DAPA-CKD and EMPA-KIDNEY established SGLT2 inhibitors as kidney-protective for all causes of CKD. CREDENCE confirmed the effect with canagliflozin in diabetic CKD. FIDELIO-DKD and FIGARO-DKD established finerenone as the third pillar alongside RAASi and SGLT2i. These results drove the KDIGO 2024 guideline update.
At-a-Glance: 5 Landmark Trials
Trial
Drug
Primary Reduction
HR (95% CI)
Journal / Year
DAPA-CKD
Dapagliflozin 10 mg
39% ↓ CKD progression + death
0.61 (0.51–0.72)
NEJM 2020
EMPA-KIDNEY
Empagliflozin 10 mg
28% ↓ kidney progression + CV death
0.72 (0.64–0.82)
NEJM 2023
CREDENCE
Canagliflozin 100 mg
34% ↓ composite CKD endpoint
0.66 (0.53–0.81)
NEJM 2019
FIDELIO-DKD
Finerenone 10–20 mg
18% ↓ kidney composite
0.82 (0.73–0.93)
NEJM 2020
FIGARO-DKD
Finerenone 10–20 mg
13% ↓ CV composite
0.87 (0.76–0.98)
NEJM 2021
DAPA-CKD Trial (2020) — The Non-Diabetic CKD Breakthrough
SGLT2 Inhibitor
Dapagliflozin 10 mg in CKD — Diabetic AND Non-Diabetic
39% reduction in CKD progression or death
HR 0.61 (95% CI 0.51–0.72) | p<0.001 | NNT = 19 over 2.4 years
Population: 4,304 adults, eGFR 25–75, UACR 200–5000 mg/g — both T2DM (68%) and non-diabetic (32%)
Primary endpoint: Sustained ≥50% eGFR decline, ESKD, renal death, or CV death
Key finding: Benefit extended to non-diabetic CKD (IgA nephropathy, FSGS, hypertensive nephrosclerosis) — the first SGLT2i trial to prove this
Safety: No increase in severe hypoglycaemia. DKA: 0.1% (dapagliflozin) vs 0% (placebo)
Mortality: 31% reduction in all-cause mortality (HR 0.69)
Heerspink HJL et al. NEJM 2020;383:1436–1446. PMID: 32970396
EMPA-KIDNEY Trial (2023) — Very Low eGFR Coverage
SGLT2 Inhibitor
Empagliflozin 10 mg — Down to eGFR 20
28% reduction in kidney progression or CV death
HR 0.72 (95% CI 0.64–0.82) | p<0.001 | 6,609 participants
Population: eGFR 20–45 OR eGFR 45–90 with UACR ≥200; 54% non-diabetic
Key expansion: Extended benefit to eGFR as low as 20 — the lowest covered by any SGLT2i trial
Primary endpoint: Sustained ≥40% eGFR decline, ESKD, renal/CV death
Hospitalisation: 14% reduction in heart failure hospitalisation (HR 0.86)
The EMPA-KIDNEY Collaborative Group. NEJM 2023;388:117–127. PMID: 36331190
CREDENCE Trial (2019) — The First SGLT2i CKD Trial
SGLT2 Inhibitor
Canagliflozin 100 mg in Diabetic CKD with Heavy Proteinuria
34% reduction in CKD composite endpoint
HR 0.66 (95% CI 0.53–0.81) | p=0.00001 | Trial stopped early for benefit
Population: 4,401 adults, T2DM + CKD, eGFR 30–90, UACR 300–5000 mg/g, all on RAASi
Historic significance: First dedicated kidney outcome trial for SGLT2i; stopped early due to overwhelming benefit
Heart failure: 39% reduction in hospitalisation for heart failure or CV death
Perkovic V et al. NEJM 2019;380:2295–2306. PMID: 30990260
KDIGO 2024: Recommends adding finerenone to RAASi + SGLT2i for CKD + T2DM with UACR >30 and eGFR ≥25
Bakris GL et al. (FIDELIO) NEJM 2020;383:2219–2229. | Pitt B et al. (FIGARO) NEJM 2021;385:2252–2263.
🧬 Apply This Evidence to Your CKD — Free
CKDPartner's multi-LLM deliberation engine interprets your lab values against these trial populations to answer whether you may benefit from SGLT2i, Finerenone, or RAASi initiation.
DAPA-CKD (NEJM 2020) proved dapagliflozin reduces CKD progression by 39% (HR 0.61) and all-cause mortality by 31% — in both diabetic and non-diabetic CKD patients. This was the first trial to confirm SGLT2i benefit beyond diabetes, establishing their use across all CKD causes.
What is the EMPA-KIDNEY trial?
EMPA-KIDNEY (NEJM 2023) showed empagliflozin reduces kidney progression by 28% (HR 0.72) in patients with eGFR as low as 20. It extended SGLT2i benefit to the broadest CKD population yet, including non-diabetic patients down to very low eGFR.
What did FIDELIO-DKD show?
FIDELIO-DKD (NEJM 2020) established finerenone as a kidney- and heart-protective drug in diabetic CKD, reducing kidney composite by 18% (HR 0.82) on top of RAASi. It is now the basis for KDIGO 2024's recommendation to add finerenone as the third pillar of CKD + T2DM therapy.