Table 6:
Summary of trials on SGLT2 inhibitors with kidney outcomes in patients with and without type 2 diabetes.
| Trial | CREDENCE (n=4,401) | CANVAS Program (n=10,142) | EMPA-REG OUTCOME (n=7,020) | DECLARE-TIMI 58 (n=17,160) | DAPA-CKD (n=4,304) |
|---|---|---|---|---|---|
| Study or Participant Characteristics | |||||
| Inclusion criteria | eGFR 30–<90 ml/min/1.73 m2; UACR >300–5000 mg/g | eGFR ≥30 ml/min/1.73 m2 | eGFR ≥30 ml/min/1.73 m2 | CLcr ≥60 ml/min | eGFR 25–75 ml/min/1.73 m2; UACR 200–5,000 mg/g |
| SGLT2i | Canagliflozin | Canagliflozin | Empagliflozin | Dapagliflozin | Dapagliflozin |
| Median follow-up, y | 2.6 | 2.4 | 3.1 | 4.2 | 2.4 |
| Baseline ACEI or ARB use | 4,395 (99.9%) | 8,116 (80%) | 5,666 (81%) | 13,950 (81%) | 1354 (31%)a; 2,870 (67%)b |
| eGFR | |||||
| ≥90 ml/min/1.73 m2 | 0 (0%) | 2,476 (24%) | 1,538 (22%) | 8,162 (48%) | 0 (0%) |
| 60–<90 ml/min/1.73 m2 | 1,809 (41%) | 5,625 (55%) | 3,661 (52%) | 7,732 (45%) | 454 (11%) |
| 45–<60 ml/min/1.73 m2 | 1,279 (29%) | 1,485 (15%) | 1,249 (18%) | 1,265 (7%) | 1,328 (31%) |
| 30–<45 ml/min/1.73 m2 | 1,313 (30%) | 554 (5%) | 570 (8%) | N/A | 1,898 (44%) |
| <30 ml/min/1.73 m2 | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 624 (14%) |
| Missing | 0 (0%) | 2 (<0.1%) | 2 (<0.1%) | 1 (<0.1%) | 0 (0%) |
| UACR | |||||
| <30 mg/g | 0 (0%) | 7,007 (69%) | 4,171 (59%) | 11,644 (68%) | n/ac |
| 30–300 mg/g | 0 (0%) | 2,266 (22%) | 2,013 (29%) | 4,030 (24%) | n/a |
| >300 mg/g | 4,401 (100%) | 760 (7%) | 769 (11%) | 1,169 (7%) | n/a |
| Missing | 0 (0%) | 109 (1%) | 67 (1%) | 317 (2%) | n/a |
| Relative Risk or Hazard Ratio comparing SGLT2i to placebo | |||||
| Dialysis, Tx, or death from kidney disease | 0.72 (0.54–0.97) | 0.56 (0.23–1.32) | 0.90 (0.30–2.67) | 0.42 (0.20–0.87) | N/A |
| Dialysis, Tx, or sustained eGFR < 15 mL/min/1.73 m2 ** | 0.68 (0.54–0.86) | 0.77 (0.30–1.97) | 0.60 (0.18–1.98) | 0.31 (0.13–0.79) | 0.64 (0.50–0.82) |
| Substantial loss of kidney function*; Dialysis, Tx, or sustained eGFR < 15 mL/min/1.73 m2 **; or death from kidney disease | 0.66 (0.53–0.81) | 0.53 (0.33–0.84) | 0.54 (0.40–0.75) | 0.53 (0.43–0.66) | 0.56 (0.45–0.68) |
on ACEI;
on ARB;
n=2079 (48%) with UACR>1,000 mg.
All participants in CREDENCE, CANVAS Program, EMPA-REG OUTCOME, and DECLARE-TIMI 58 were with type 2 diabetes. In DAPA-CKD, 67.5% of participants were with type 2 diabetes.
defined as a doubling of serum creatinine with the exception of DECLARE-TIMI 58 (sustained 40% decline in eGFR) and DAPA-CKD (sustained 50% decline in eGFR).
except for the EMPA-REG OUTCOME trial, which did not include sustained eGFR < 15 mL/min/1.73 m2.
Abbreviations: SGLT2i =sodium/glucose cotransporter 2 inhibitor; ACEI=angiotensin-converting-enzyme inhibitor; ARB=angiotensin-receptor blocker; eGFR=estimated glomerular filtration rate; UACR=urinary albumin-creatinine ratio; Tx, transplantation; CREDENCE, Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation; CANVAS, Canagliflozin Cardiovascular Assessment Study; EMPA-REG OUTCOME, BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; DECLARE-TIMI 58, Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58; DAPA-CKD, Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease; n/a=not available. Based on information in Neun et al 2019 (Lancet Diabetes Endocrinol, https://doi.org/10.1016/s2213-8587(19)30256-6) and Heerspink et al 2020 (NEJM, https://doi.org/10.1056/nejmoa2024816).