Table 3.
Principal baseline characteristics and major renal outcomes of interest in the recently published type 2 diabetes outcome trials.
| Trial | Drug | Population | Baseline Renal Characteristics | Renal Composite Outcome | Albuminuria | GFR/Creatinine | ESRD |
|---|---|---|---|---|---|---|---|
| EMPA-REG OUTCOME [5] | Empagliflozin | 7020 patients with T2D with GFR > 30 mL/min | 25.9% of patients had GFR <60 mL/min | Progression to macroalbuminuria, doubling of serum creatinine with GFR ≤ 45 mL/min, ESRD, renal death | Incident microalbuminuria (UACR 30–300 mg/g) Incident macroalbuminuria (UACR > 300 mg/gr) |
Doubling of serum creatinine and GFR < 45 mL/min | Need of RRT |
| CANVAS program [51] | Canagliflozin | 10142 patients with T2D and cardiovascular disease. | 20.1% of patients had GFR < 60 mL/min | Sustained ≥ 40% decrease in GFR, ESRD or renal death | New microalbuminuria or new macroalbuminuria with ≥ 30% increased UACR | Sustained 40% reduction in GFR for ≥ 30 days | Sustained GFR < 15 mL/min for > 30 days, dyalisis ≥ 30 days or renal transplant. |
| CREDENCE trial [54] | Canagliflozin | 4401 patients with T2D, GFR 30–89 mL/min and UACR 300–5000 mg/gr | All patients had GFR of 30–89 mL/min and UACR 300–5000 mg/g | Doubling of serum creatinine, ESRD, or death from renal or cardiovascular disease | Comparison of UACR versus placebo | Sustained doubling of serum creatinine | Sutained GFR < 15 mL/min for > 30 days or need for dialysis or renal transplant |
| DECLARE-TIMI 58 [52] | Dapagliflozin | 17160 patients with T2D and cardiovascular disease | 7.4% of patients had GFR ≤ 60 mL/min | Sustained ≥ 40% decrease in GFR to ≤ 60 mL/min, ESRD, renal or cardiovascular death | Comparison of UACR versus placebo | Sustained ≥ 40% decrease in FGR to ≤ 60 mL/min | Sustained GFR < 15 mL/min, or dialysis for ≥ 90 days or renal transplant |
| DAPA-HF [55] | Dapagliflozin | 4744 patients with T2D and non-T2D, HF with EF < 40% | All patients had GFR > 30 mL/min | Sustained ≥ 50% decrease in GFR, ESRD, renal death | Not reported | Sustained ≥ 50% decrease in GFR | Sustained GFR < 15 mL/min ≥ 28 days, or need for continuous RRT |
| SAVOR-TIMI [56] | Saxagliptin | 16492 patients with T2D and cardiovascular disease | 15.6% of patients had GFR < 50 mL/min | Doubling serum creatinine or ESRD | Categorical change in UACR from baseline | Doubling of serum creatinine | Need for renal dialysis, transplant or serum creatinine > 530 µmol/L |
| CARMELINA trial [43] | Linagliptin | 6979 patients with T2D and high cardiovascular and renal risk | 74% of patients had GFR of 30–59 mL/min and 15.2% had GFR < 30 mL/min | Sustained ≥ 40% decrease in GFR and GFR ≤ 60 mL/min, ESRD, renal death | Microalbuminuria (ACR 30–300 mg/gr) or macroalbuminuria (UACR ≥ 300 mg/g) | Sustained ≥ 40% decrease in GFR and GFR ≤ 60 mL/min | Need for renal dialysis ≥ 30 days or renal transplant |
| LEADER trial [6] | Liraglutide | 9340 patients with T2D | 23.1% of patients had GFR < 60 mL/min | New macroalbuminuria, doubling of serum creatinine with GFR ≤ 45 mL/min, need for continuous RRT or renal death | New macroalbuminuria (UACR > 300 mg/gr or urinary albumin > 300 mg/24 h) | Doubling of the serum creatinine with GFR ≤ 45 mL/min | Need for continuous RRT |
| SUSTAIN-6 trial [44] | Semaglutide | 3297 patients with T2D and Cardiovascular disease | 28.5% of patients had FGR < 60 mL/min | New macroalbuminuria, doubling of serum creatinine with GFR ≤ 45 mL/min, need for continuous RRT or renal death | New macroalbuminuria (UACR > 300 mg/gr or urinary albumin > 300 mg/24 h) | Doubling of the serum creatinine with GFR ≤ 45 mL/min | Need for continuous RRT |
| EXSCEL trial [47] | Exenatide | 14752 patients with T2D | 21.6% of patients had GFR < 60 mL/min | New macroalbuminuria sustained ≥ 40% decrease in GFR or RRT or renal death | New macroalbuminuria | Sustained ≥ 40% decrease in GFR | Need for continuous RRT |
| REWIND study [46] | Dulaglutide | 9901 patients with T2D | 22.2% of patients had GFR < 60 mL/min | New macroalbuminuria, sustained ≥ 30% decrease in GFR or chronic RRT | New macroalbuminuria (UACR > 33.9 mg/mmol) | Sustained ≥ 30% decrease in GFR | Need for continuous RRT |
| FIDELIO-DKD [57] | Finerenone | 5734 patients with CKD and T2D | All patients had GFR of 25–60 mL/min and UACR of 300–5000 mg/g | Kidney failure, sustained ≥ 40% decrease in GFR or death from renal causes | Change in UACR from baseline to month 4 | Sustained ≥ 40% decrease in GFR | GFR < 15 mL/min or initiation of RRT (≥ 90 days) or kidney transplantation |
GFR: glomerular filtration rate; ESRD: end-stage renal disease; UACR: urinary albumin/creatinine ratio; T2D: type 2 diabetes; RRT: renal replacement therapy.