Geographic and racial variability in kidney, cardiovascular and safety outcomes with canagliflozin: A secondary analysis of the CREDENCE randomized trial

Abstract Aim To explore the effect of canagliflozin on kidney and cardiovascular events and safety outcomes in individuals with type 2 diabetes and chronic kidney disease across geographic regions and racial groups. Materials and Methods A stratified Cox proportional hazards model was used to assess efficacy and safety outcomes by geographic region and racial group. The primary composite outcome was a composite of end‐stage kidney disease (ESKD), doubling of the serum creatinine (SCr) level, or death from kidney or cardiovascular causes. Secondary outcomes included: (i) cardiovascular death or heart failure (HF) hospitalization; (ii) cardiovascular death, myocardial infarction (MI) or stroke; (iii) HF hospitalization; (iv) doubling of the SCr level, ESKD or kidney death; (v) cardiovascular death; (vi) all‐cause death; and (vii) cardiovascular death, MI, stroke, or hospitalization for HF or for unstable angina. Results The 4401 patients were divided into six geographic region subgroups: North America ( n = 1182, 27%), Central and South America ( n = 941, 21%), Eastern Europe ( n = 947, 21%), Western Europe ( n = 421, 10%), Asia ( n = 749, 17%) and Other ( n = 161, 4%). The analyses included four racial groups: White ( n = 2931, 67%), Black or African American ( n = 224, 5%), Asian ( n = 877, 20%) and Other ( n = 369, 8%). Canagliflozin reduced the relative risk of the primary composite outcome in the overall trial by 30% (hazard ratio 0.70, 95% confidence interval 0.59‐0.82; P = 0.00001). Across geographic regions and racial groups, canagliflozin consistently reduced the primary composite endpoint without evidence of heterogeneity (interaction P values of 0.39 and 0.91, respectively) or significant safety outcome differences. Conclusions Canagliflozin reduces the risk of kidney and cardiovascular events similarly across geographic regions and racial groups.