Table 3 RCTs evaluating SGLT2is in patients with CKD (with or without T2DM)
Trial acronym | EMPA-KIDNEY | SCORED | CREDENCE | DAPA-CKD |
|---|---|---|---|---|
Trial name | Study of heart and kidney protection with empagliflozin | Effect of sotagliflozin on cardiovascular and renal events in participants with type 2 Diabetes and Moderate renal impairment who are at cardiovascular risk | Canagliflozin and renal events in diabetes with established nephropathy Clinical Evaluation | Dapagliflozin and prevention of adverse outcomes in chronic kidney disease |
Therapeutic area | CKD (HF, 10% patients; T2DM, 44% patients; HF + T2DM, 14% patients) | CKD (HF, 31% patients; EF, ≥ 50% 16% patients) | CKD (HF, ~ 15% patients) | CKD (HF, ~ 11% patients; T2DM, 67%) |
ClinicalTrials.gov identifier | NCT03594110 | NCT03315143 | NCT02065791 | NCT03036150 |
ClinicalTrials.gov URL | ||||
Trial completion | Jan 2025 (primary outcome completion Jul 2022) | Jul 2020 (terminated due loss of sponsor funding) | Oct 2018 | Jun 2020 |
Publication | EMPA-KIDNEY Collaborative Group, N Engl J Med 2022 [80] EMPA-KIDNEY Collaborative Group, Nephrol Dial Transplant 2022 [79] | Bhatt et al., N Engl J Med 2021 [76] | Perkovic et al., N Engl J Med 2019 [77] | Heerspink et al., N Engl J Med 2020 [78] |
Intervention (once daily) | Empagliflozin 10 mg vs. PBO | Sotagliflozin 200–400 mg vs. PBO | Canagliflozin 100 mg vs. PBO | Dapagliflozin 10 mg vs. PBO |
eGFR inclusion (mL/min/1.73 m2) |  ≥ 20 to < 45 or ≥ 45 to < 90 with UACR ≥ 200 mg/g (or protein:creatinine ≥ 300 mg/g) |  ≥ 25 to ≤ 60 |  ≥ 30 and < 90 |  ≥ 25 to ≤ 75 |
Other relevant inclusion criteria | None | T2DM, HbA1c ≥ 7% | T2DM, HbA1c ≥ 6.5% and ≤ 12.0% UACR > 300 mg/g and ≤ 5000 mg/g Aged ≥ 30 years | With/without T2DM UACR ≥ 200 to ≤ 5000 mg/g |
Population | Randomized = 6609 (empagliflozin, 3304; PBO, 3305) | Randomized = 10,584 (sotagliflozin, 5292; PBO, 5292) | Randomized = 4401 (canagliflozin, 2202; PBO, 2199) | Randomized = 4304 (dapagliflozin, 2152; PBO, 2152) |
Trial duration | Median 2.0Â years | Median 16Â months | Median 2.6Â years (trial stopped early due to clear benefit observed for primary outcome) | Median 2.4Â years |
Primary endpoint | Composite of kidney disease progression (ESKD, sustained decline in eGFR to < 10 mL/min/1.73m2, sustained decline of ≥ 40% in eGFR from randomization, or renal death) or CV death | Total number of CV deaths, HF hospitalizations, and urgent HF visits | Composite of doubling of serum creatinine, ESKD, renal or CV death | Composite of ≥ 50% decrease in eGFR, ESKD, renal or CV death |
Primary endpoint achieved? | Yes | Yes | Yes | Yes |
Details | 28% reduced risk of primary outcome with empagliflozin (13.1% vs. 16.9% in PBO group; HR: 0.72; 95% CI 0.64–0.82; p < 0.001) | 26% reduced risk of primary outcome (events per 100 PY) with sotagliflozin (5.6 vs. 7.5 in PBO group; HR: 0.74, 95% CI 0.63–0.88; p < 0.001) | 30% reduced risk of primary outcome (events per 1000 PY) with canagliflozin (43.2 vs. 61.2 in PBO group; HR: 0.70, 95% CI 0.59–0.82; p < 0.00001) | 39% reduced risk of primary outcome with dapagliflozin (9.2% vs. 14.5% in PBO group; HR: 0.61, 95% CI 0.51–0.72; p < 0.001) |
Other kidney endpoint | See primary endpoint | Secondary endpoint (revised): composite of first occurrence of sustained decrease ≥ 50% in eGFR from baseline for ≥ 30 days, long-term dialysis, renal transplantation, or sustained eGFR of < 15 mL/min/1.73 m2 for ≥ 30 days | Secondary endpoint: composite of ESKD, doubling of serum creatinine, or renal death | Secondary endpoint: composite of ≥ 50% decrease in eGFR, ESKD, or renal death |
Other kidney endpoint achieved? | See primary endpoint | No | Yes | Yes |
Details |  | Composite endpoint (events per 100 PY): Sotagliflozin 0.5 vs. PBO 0.7 (HR: 0.71, 95% CI 0.46–1.08; p value NA, as not included in hierarchical-testing strategy) | 34% reduced risk of composite endpoint (events per 1000 PY) with canagliflozin (27.0 vs. 40.4 in PBO group; HR: 0.66, 95% CI 0.53–0.81; p < 0.001) | 44% reduced risk of composite endpoint with dapagliflozin (6.6% vs. 11.3% in PBO group; HR: 0.56, 95% CI 0.45–0.68; p < 0.001) |
HF endpoint | Secondary endpoint: composite of HHF or CV death | Secondary endpoint: total number HHF and urgent HF visits | Secondary endpoint: composite of HHF or CV death | Secondary endpoint: composite of HHF or CV death |
HF endpoint achieved? | No | Yes | Yes | Yes |
Details | Composite endpoint: empagliflozin 4.0% vs. PBO 4.6% (HR: 0.84, 95% CI 0.67–1.07; p = 0.15) | 33% reduced risk of endpoint (events per 100 PY) with sotagliflozin (3.5 vs. 5.1 in PBO group; HR: 0.67, 95% CI 0.55–0.82; p < 0.001) | 31% reduced risk of endpoint (events per 1000 PY) with canagliflozin (31.5 vs. 45.4 in PBO group; HR: 0.69, 95% CI 0.57–0.83; p < 0.001) | 29% reduced risk of composite endpoint with dapagliflozin (4.6% vs. 6.4% in PBO group; HR: 0.71, 95% CI 0.55–0.92; p < 0.009) |