Table 2.
Renal outcome trials with sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus
| Parameters | Canagliflozin [45] | Dapagliflozin [89] | Dapagliflozin [61] |
|---|---|---|---|
| Study acronym (NCT number/ClinicalTrials.gov identifier) | CREDENCE (NCT02065791) | DELIGHT (NCT02547935) | DERIVE(NCT02413398) |
| Number of enrolled patients | 4401 | 461 | 321 |
| Median observation time/ follow-up period | 2.62 years | 24 weeks | 24 weeks |
| Eligibility |
eGFR = 30 to < 90 mL/min/1.73 m2 ACR > 300 to 5000 Treatment with RAAS blockade |
1. HbA1c ≥ 7.0% and ≤ 11.0% 2. Stable antidiabetic treatment during the last 12 weeks up to randomization 3. eGFR 25–75 mL/min/1.73 m2, inclusive 4. Micro- or macroalbuminuria (urine ACR 30—3500 mg/g) 5. Treatment with ACE-I or an ARB for at least 3 months prior to screening |
HbA1c ≥ 7.0% and ≤ 11.0% Renal impairment: CKD 3A |
| Intervention | Cana 100 mg once daily |
Dapa 10 mg or Dapa 10 mg + saxagliptin 2.5 mg |
Dapa 10 mg |
| Control | Placebo | Placebo | Placebo |
| Renal outcomes | |||
| Composite of ESKD, a doubling of the serum creatinine level, or death from renal, or CV causes |
Events per 1000 patient-years: Cana: 43.2 HR 0.70 (95% CI 0.59–0.82, p < 0.00001) |
Not reported | Not reported |
| Change from baseline in urine ACR at Week 24 | Not reported |
Difference versus placebo at Week 24: Dapa − 21.0% (95% CI − 34.1 to − 5.2, p = 0.011) Dapa + saxagliptin − 38.0% (95% CI − 48.2 to − 25.8, p < 0.0001) |
Change from baseline in urine ACR at Week 24 for patients with baseline urine: ACR ≥ 30 mg/g Week 12: difference − 41.7% (95% CI − 57.1 to − 21.0, p < 0.001) Week 24: difference: − 14.0% 95% CI − 42.3, 28.0, p = 0.454 |
| Change from baseline in eGFR at Week 24 | Not reported |
Difference versus placebo at Week 24: Dapa − 2.35 mL/min/1.73 m2 (95% CI − 4.16 to − 0.53, p = 0.011) Dapa + saxagliptin − 2.44 mL/min/1.73 m2 (95% CI − 4.22 to − 0.66, p = 0.0075) |
Difference vs placebo: − 2.49 mL/min/1.73 m2 (95% CI − 4.96 to − 0.02) |
| Doubling of serum creatinine level |
Events per 1000 patient-years: Cana: 20.7 HR 0.60 (95% CI 0.48–0.76, p < 0.001) |
Not reported | Not reported |
| ESKD |
Events per 1000 patient-years: Cana: 20.4 HR 0.68 (95% CI 0.54–0.86, p = 0.002) |
Not reported | Not reported |
| eGFR < 15 mL/min/1.73 m2 |
Events per 1000 patient-years: Cana: 13.6 HR 0.60 (95% CI 0.45–0.80) |
Not reported | Not reported |
| Dialysis initiated or kidney transplantation |
Events per 1000 patient-years: Cana: 13.3 HR 0.74 (95% CI 0.55–1.00) |
Not reported | Not reported |
| Renal death |
Events per 1000 patient-years: Cana: 0.3 |
Not reported | Not reported |
| ESKD, doubling of serum creatinine level, or renal death |
Events per 1000 patient-years: Cana: 27.0 HR 0.66 (95% CI 0.53–0.81) |
Not reported | Not reported |
| Dialysis, kidney transplantation, or renal death |
Events per 1000 patient-years: Cana: 13.6 HR 0.72 (95% CI 0.54–0.97) |
Not reported | Not reported |
ACE-I Angiotensin-converting enzyme inhibitor, ACR albumin:creatinine ratio, ARB angiotensin II receptor blocker, ESKD end-stage kidney disease RAAS renin-angiotensin aldosterone system