Ethnic disparities in cardiovascular and renal responses to canagliflozin between Asian and White patients with type 2 diabetes mellitus: A post hoc analysis of the CANVAS Program

Abstract Aim To assess the potential heterogeneity in cardiovascular (CV), renal and safety outcomes of canagliflozin between Whites and Asians, as well as these outcomes in each subgroup. Materials and Methods The CANVAS Program enrolled 10 142 patients with type 2 diabetes, comprising 78.34% Whites and 12.66% Asians. CV, renal and safety outcomes were comprehensively analysed using Cox regression models, while intermediate markers were assessed using time‐varying mixed‐effects models. Racial heterogeneity was evaluated by adding a treatment‐race interacion term. Results Canagliflozin showed no significant racial disparities in the majority of the CV, renal and safety outcomes. The heterogeneity ( p = .04) was observed on all‐cause mortality, with reduced risk in Whites (hazard ratio 0.84; 95% confidence interval 0.71‐0.99) and a statistically non‐significant increased risk in Asians (hazard ratio 1.64; 95% confidence interval 0.94‐2.90). There was a significant racial difference in acute kidney injury ( p = .04) and a marginally significant racial heterogeneity for the composite of hospitalization for heart failure and CV death ( p = .06) and serious renal‐related adverse events ( p = .07). Conclusion Canagliflozin reduced CV and renal risks similarly in Whites and Asians; however, there was a significant racial discrepancy in all‐cause mortality. This distinction may be attributed to the fact that Asian patients exhibited diminished CV protection effects and more renal adverse events with canagliflozin, potentially resulting from the smaller reductions in weight and uric acid. These findings highlight the importance of investigating the impact of race on treatment response to sodium‐glucose cotransporter‐2 inhibitors and provide more precise treatment strategies.