Table 1:
Main: clinical trials evaluating cardiorenal outcomes in patients treated with SGLT2i. CKD: chronic kidney disease; MACE: major adverse cardiovascular event (CV death, nonfatal MI, or nonfatal stroke); CV: cardiovascular; eGFR: estimated GFR; HF: heart failure; HHF: hospitalised heart failure; EF: ejection fraction; ESKD: end-stage kidney disease; T2DM Type Diabetes mellitus.
| Trials (ref) | Year of completion | SGLT2i | Patient population | Number of patients | Median follow up | Mean eGFR (ml/min/1.73 m2) | Μedian uACR mg/g (IQR) | CV outcome | SGLT2i vs. placebo group | HR (95%CI) | Renal outcome | SGLT2i vs. placebo group | HR (95%CI) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMPA-REG OUTCOME [48] | 2015 | empagliflozin (10 or 25 mg) | T2DM and CVD | 7020 | 3.1 years(2.6 treatment) | 74 ± 21 | ΝΑ(28.7% microalbuminuria and 11% macroalbuminuria) | MACEHF or CVdeath (excluding fatal stroke)CV death | 10.5% vs. 12.1%5.7% vs. 8.5%3.7% vs. 5.9 | 0.86(0.74–0.99)0.66 (0.55–0.79)0.62(0.49–0.77) | (Post hoc)Incident or worsening nephropathy or CV deathincident orworsening nephropathydoubling of the serum creatinineinitiation of renal-replacement therapy | 16.2% vs. 23.6%12.7% vs 18.8%1.5% vs. 2.6%0.3% vs. 0.6% | 0.61 (0.55–0.69)0.61 (0.53–0.7)0.56 (0.39–0.79)0.45 (0.21–0.97) |
| CANVAS [17] | 2017 | canagliflozin(100 or 300 mg) | T2D andhigh CVD risk | 10 142 | 2.6 years | 76. 5 ± 20. 5 | 12.3 (6.65–42.1) | MACEHospitalization for HF | 26.9% vs. 31.5%5.5 vs. 8.68 per 1000 patient-years | 0.86(0.75–0.97)0.67 (0.52–0.87) | progression of albuminuriasustained 40% reduction in eGFR, need for renal-replacement therapy, or death from renal causes | 89.4 vs. 128.7per 1000 patient-years5.5 vs. 9.0 | 0.73 (0.67–0.79)0.60 (0.47–0.77) |
| DECLARE-TIMI58 [20] | 2018 | Dapagliflozin(10 mg) | T2DMand ≥ 1 CVDrisk factor | 17.160 | 4.2years | 85.2 ± 16 | NA | MACECV death or hospitalization for HF | 8.8 vs. 9.4%4.9% vs. 5.8% | 0.93 (0.84–1.03)0.83 (0.73–0.95) | ≥40% reduction in eGFR, ESKD≥90 days, (dialysis, sustained eGFR <15 ml/min/1.73 m2, orkidney transplantation), or renal/CV death | 4.3% vs. 5.6% | 0.76 (0.67–0.87) |
| CREDENCE [18] | 2019 | canagliflozin(100 mg) | T2DM and CKD | 4401 | 2.6 years | 56.2 ± 18.2 | 927 [463–1833] | MACEHHF or CVdeath | 9.9 vs. 12.2%8.1 vs. 11.5% | 0.80 (0.67–0.95)0.69 (0.57–0.83) | doubling ofserum creatinine, ESKD (dialysis, renal transplantation, or sustainedeGFR <15 ml/min/1.73 m2), or renal/CV death | 11.1% vs. 15.4% | 0.70 (0.59–0.82) |
| VERTIS CV [80] | 2019 | ertugliflozin(5 or 15 mg) | T2D and established CVD | 8246 | 3.5 years | 76.1 ± 20.9(75.7 ± 20.8 placebo group) | NA | hospitalization for heartfailureDeath from CV causes or hospitalizationfor HF | 11.9% vs. 11.9%8.1% vs. 9.1% | 0.97 (0.85–1.11)0.88 (0.75–1.03) | death from renal causes,renal-replacement therapy, or doubling of theserum creatinine | 3.2% vs. 3.9% | 0.81 (0.63–1.04) |
| EMPEROR reduced [50] | 2020 | empagliflozin(10 mg) | HF with reduced EF | 3730 | 16 months | 61.8 ± 21.7 (62.2 ± 21.5 placebo group) | NA | death fromCV causes or hospitalization for HFhospitalization for HF | 19.4% vs24.7%20.8% vs. 29.6% | 0.75 (0.65–0.86)0.70 (0.58–0.85) | dialysis or renal transplantation orsustained reduction in the eGFReGFR decline | 1.6% s 3.1%–0.93 vs. –4.21 ml perminute per 1.73 m2 | 0.50 (0.32–0.77)(95%CI –1.97–0.11) and(95% CI, −5.26 to −3.17) |
| EMPEROR –preserved [51] | 2021 | empagliflozin(10 mg) | HF with preserved EF | 5988 | 26.2 months | 60.6 ± 19.8 | NA | death fromCV causes or hospitalization for HFhospitalization for HF | 13.8% vs. 17.1%8.6% vs. 11.8% | 0.79 (0.69–0.90)0.73 (0.61–0.83) | Rate of declinein the eGFR | (−1.25 vs. −2.62 ml per minute per 1.73 m2 per year | |
| DAPA-CKD [35] | 2020 | dapagliflozin(10 mg) | CKD (T2D and non-diabetics) | 4304 | 2.4 years | 43.1 ± 12.4 | 965 (472–1903)934 (482–1868) for the placebo group | Death CV causes or hospitalization for HF | 4.6% vs. 6.4% | 0.71 (0.55–0.92) | decline in e-GFR of at least 50%, ESKD, or death from renal, or CV causessustained decline in the eGFR of at least 50%, ESKD, or death from renal causes | 9.2% vs. 14.5%6.6% vs. 11.3% | 0.61 (0.51 −0.72)0.56 (0.45–0.68) |
| EMPA-KIDNEY [58] | 2022 | Empagliflozin(10 mg) | CKD (T2D and non-diabetics) | 6609 | 2.0 years | 37.5 ± 14.8 | 412 (94–1190) | hospitalization for HF or cardiovascular death | 4.0% vs. 4.6% | 0.84 (0.67–1.07) | ESKD, a sustained decline in eGFR to < 10 mL/min/1.73m², renal death, or a sustained decline of ≥ 40% in eGFR from randomization) or (ii) Cardiovascular death | 13.1% vs. 16.9% | 0.72 (0.64–0.82) |