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Kidney protection with canagliflozin: A combined analysis of the randomized CANVAS program and CREDENCE trials
Vikas S Sridhar1,2,3, Brendon L Neuen4,5, Robert A Fletcher4
1Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
Aim:
In the CANVAS Program and CREDENCE trials, the sodium glucose co-transporter 2 inhibitor canagliflozin reduced the risk of cardiovascular and kidney events in patients with type 2 diabetes. The current study analysed a pooled population to ascertain the kidney protection provided by canagliflozin across the full spectrum of kidney parameters.
Methods:
This post-hoc pooled analysis of the CANVAS Program (N = 10 142) and CREDENCE trial (N = 4401), assessed the risk of the primary kidney composite (doubling of serum creatinine, end-stage kidney disease, renal death), in all patients and subgroups defined by baseline estimated glomerular filtration rate (<30, 30 to <45, 45 to <60 and ≥60 ml/min/1.73 m2 ), albuminuria [<30, 30-300, >300 mg/g (<3.39, 3.39-33.9, >33.9 mg/mmol)] and 2012 Kidney Disease: Improving Global Outcomes (KDIGO) classification of chronic kidney disease (low/moderate, high and very high risk).
Results:
In the overall population, the risk for the primary kidney composite outcome was 37% lower in the canagliflozin group versus placebo (HR: 0.63; 95% CI: 0.53, 0.77; p < .001). There was no evidence of heterogeneity in the kidney protective effects of canagliflozin across a range of kidney risks when stratified by baseline estimated glomerular filtration rate, albuminuria or KDIGO risk category (all pinteraction > .05). A statistically significant risk reduction of the primary kidney composite outcome was sustained by approximately 18 months after randomization.
Conclusions:
These results emphasize a critical role of canagliflozin in kidney protection across a broad spectrum of participants with type 2 diabetes with varying levels of kidney function.
Insights
Canagliflozin significantly reduced kidney events in patients with type 2 diabetes. This sodium-glucose co-transporter 2 inhibitor demonstrated consistent kidney protection across diverse patient subgroups, highlighting its therapeutic potential.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Type 2 diabetes is a leading cause of chronic kidney disease.
- Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown cardiovascular and renal benefits.
- Canagliflozin's kidney protective effects require further elucidation across varied kidney function levels.
Purpose of the Study:
- To evaluate the kidney protective efficacy of canagliflozin.
- To assess canagliflozin's effects on kidney composite outcomes.
- To analyze kidney protection across subgroups defined by kidney function and albuminuria.
Main Methods:
- Pooled analysis of the CANVAS Program and CREDENCE trials.
- Inclusion of over 14,000 patients with type 2 diabetes.
- Assessment of primary kidney composite outcome (doubling of serum creatinine, end-stage kidney disease, renal death).
- Subgroup analyses based on estimated glomerular filtration rate, albuminuria, and KDIGO risk classification.
Main Results:
- Canagliflozin reduced the risk of the primary kidney composite outcome by 37% (HR: 0.63; p < .001).
- No significant heterogeneity in kidney protection was observed across baseline estimated glomerular filtration rate, albuminuria, or KDIGO risk categories.
- Risk reduction was sustained for approximately 18 months post-randomization.
Conclusions:
- Canagliflozin provides significant kidney protection in patients with type 2 diabetes.
- The benefits of canagliflozin are consistent across a wide spectrum of kidney function and risk levels.
- Canagliflozin plays a critical role in managing kidney disease in type 2 diabetes patients.
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