Canagliflozin Linked to Reduction in Renal, CV Events Across Geographic Regions

Data show event rates varied two-fold across regions, with risk reduction of T2D and CKD events across geographic regions without heterogeneity.

A new study at the 2021 American Diabetes Association Virtual Meeting presented data from the CREDENCE trial, showing canagliflozin was associated with a reduction in kidney and cardiovascular (CV) events in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).

Investigators, led by Kathryn Cardoza, MD, Stanford University, aimed to determine if the results show the same efficacy of canagliflozin reduction in T2D and CKD events across geographic regions.

They found event rates varied two-fold across regions, while canagliflozin reduced the risk of T2D and CKD events across geographic regions without heterogeneity.

Study

The CREDENCE study was a multicenter, randomized, double-blind, placebo-controlled clinical trial comparing canagliflozin to placebo.

It had a median follow up-time of 2.6 years and took place in 690 sites over 34 countries divided into 6 geographic regions.

The 6 geographic regions included North America (27%), Eastern Europe (21%), Central/South America (21%), Asia (17%), Western Europe (10%), and Other (4%).

Investigators used a Cox proportional-hazards model to analyze the primary outcome and secondary outcomes.

The primary outcome consisted of a composite of end-stage kidney disease (dialysis, transplantation, or a sustained eGFR of <15 mL/min/1.72 m2), doubling of serum Cr, or death from renal or CV causes.

Results

Data show a total of 4401 participants were enrolled across North America (n = 1182), Central and South America (n = 941), Eastern Europe (n = 947), Western Europe (n = 421), Asia (n = 749) and Other (n = 161).

At baseline, the mean age was 63 years, with 34% female patients and 97% of patients experiencing hypertension and 50% of patients experiencing cardiovascular disease (CVD). The baseline eGFR was found to be 56.2 ± 18.2 mL/min/1.72 m2.

Investigators found canagliflozin reduced the risk of the primary composite outcome in the overall trial by 30%.

Data show the overall event rate was 43.2 events per 1000 patient-years with canagliflozin, compared to 61.2 events per 1000 patient-years with placebo.

The team noted that placebo events had a wide range with 31.8 events per 1000 patient-years in Western Europe (HR 0.73; 95% CI, 0.36 - 1.47), compared to 77.2 events per 1000 patient-years in Asia (HR 0.59; 95% CI, 0.40 - 0.87) and 80.5 events per 1000 patient-years in Other (HR 0.40; 95% CI, 0.15 - 1.02).

Further, the Asia and Other categories had the largest decrease in event rate in canagliflozin compared to placebo at 46.7 events per 1000 patient-years and 28.1 events per 1000 patient-years compared to 77.2 events per 1000 patient-years and 80.5 events per 1000 patient-years, respectively.

The team noted individual components of the primary composite outcome, including ESKD, doubling of serum creatine, and death from renal of CV causes.

As seen in the overall data on ESKD, canagliflozin resulted in 20.4 events per 1000 patient-years, while placebo resulted in 29.4 events per 1000 patient-years.

Further, data show in doubling of serum creatine, canagliflozin had a 20.7 event rate and placebo had a 33.8 event rate. In death from renal or CV causes, canagliflozin had a 19.4 event rate, compared to placebo with a 25.2 event rate.

In secondary composite outcomes of doubling of serum creatine, ESKD, or death and CV death or hospitalization for heart failure, investigators found canagliflozin reduced the relative risk by 34% and 31%, respectively. Across all regions, canagliflozin reduced secondary endpoint risk.

No difference was observed between canagliflozin and placebo in safety outcomes.

Conclusion

Investigators concluded canagliflozin resulted in a reduction in both kidney and cardiovascular events across geographic regions, noting no evidence of heterogeneity.

“Event rates for the primary composite outcome varied two-fold across regions and needs further study,” investigators wrote.

The study, “Canagliflozin Improves Cardiovascular and Renal Outcomes Across Broad Geographical Regions: Results from CREDENCE,” was published online by ADA.