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Updated: Aug 23, 2025
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Cardiovascular Effects of Canagliflozin in Relation to Renal Function and Albuminuria
Ashish Sarraju1, George Bakris2, Christopher P Cannon3
1Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Insights
Canagliflozin effectively reduced cardiovascular death or heart failure hospitalization in type 2 diabetes patients. These benefits were consistent across various levels of kidney function and albuminuria, highlighting its broad efficacy.
Area of Science:
- Cardiology
- Nephrology
- Endocrinology
Background:
- Patients with type 2 diabetes mellitus (T2DM) face elevated cardiovascular (CV) risk, including hospitalization for heart failure (HHF).
- Canagliflozin has demonstrated efficacy in reducing CV and kidney events in T2DM patients with high CV risk or nephropathy within the CANVAS Program and CREDENCE trial.
Purpose of the Study:
- To evaluate the impact of canagliflozin on cardiovascular outcomes.
- To assess these effects based on baseline estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) using pooled data from the CANVAS Program and CREDENCE trial.
Main Methods:
- Pooled patient-level data from 14,543 participants in the CANVAS Program and CREDENCE trial were analyzed.
- Canagliflozin's effects on CV death or HHF were assessed across eGFR (<45, 45-60, >60 mL/min/1.73 m²) and UACR (<30, 30-300, >300 mg/g) subgroups.
- Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs).
Main Results:
- Higher rates of CV death or HHF were observed with declining eGFR and/or increasing UACR.
- Canagliflozin significantly reduced CV death or HHF versus placebo (19.4 vs 28.0 events per 1,000 patient-years; HR: 0.70; 95% CI: 0.62-0.79).
- Consistent benefits of canagliflozin were observed across all eGFR and UACR categories, with no significant interaction (P > 0.40).
Conclusions:
- Cardiovascular risk, defined by CV death or HHF, is elevated in patients with lower baseline eGFR and/or higher UACR.
- Canagliflozin demonstrated consistent efficacy in reducing CV death or HHF among participants with T2DM and high CV risk or nephropathy.
- The benefits of canagliflozin were independent of baseline renal function and albuminuria levels.
Background:
People with type 2 diabetes mellitus (T2DM) have elevated cardiovascular (CV) risk, including for hospitalization for heart failure (HHF). Canagliflozin reduced CV and kidney events in patients with T2DM and high CV risk or nephropathy in the CANVAS (CANagliflozin cardioVascular Assessment Study) Program and the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial.
Objectives:
The aim of this study was to assess the effects of canagliflozin on CV outcomes according to baseline estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) in pooled patient-level data from the CANVAS Program and CREDENCE trial.
Methods:
Canagliflozin effects on CV death or HHF were assessed by baseline eGFR (<45, 45-60, and >60 mL/min/1.73 m2) and UACR (<30, 30-300, and >300 mg/g). HRs and 95% CIs were estimated by using Cox regression models overall and according to subgroups.
Results:
A total of 14,543 participants from the CANVAS Program (N = 10,142) and the CREDENCE (N = 4,401) trial were included, with a mean age of 63 years, 35% female, 75% White, 13.2% with baseline eGFR <45 mL/min/1.73 m2, and 31.9% with UACR >300 mg/g. Rates of CV death or HHF increased as eGFR declined and/or UACR increased. Canagliflozin significantly reduced CV death or HHF compared with placebo (19.4 vs 28.0 events per 1,000 patient-years; HR: 0.70; 95% CI: 0.62-0.79), with consistent results across eGFR and UACR categories (all P interaction >0.40).
Conclusions:
Risk of CV death or HHF was higher in those with lower baseline eGFR and/or higher UACR. Canagliflozin consistently reduced CV death or HHF in participants with T2DM and high CV risk or nephropathy regardless of baseline renal function or level of albuminuria. (Canagliflozin Cardiovascular Assessment Study [CANVAS], NCT01032629; A Study of the Effects of Canagliflozin [JNJ-24831754] on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus [CANVAS-R], NCT01989754; and Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy [CREDENCE], NCT02065791).
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