Is canagliflozin effective in lowering the risk of all-cause mortality in adults with type 2 diabetes compared to the placebo?

OBJECTIVE: The objective of this selective EBM review is to determine whether or not “canagliflozin is effective in lowering the risk of all-cause mortality in adults with type 2 diabetes compared to the placebo?” STUDY DESIGN: A systematic review of three English language, primary, double-blind, randomized controlled trials published from 2013 to 2019. DATA SOURCES: All primary studies were published in peer reviewed journals and selected through PubMed and Cochrane databases comparing canagliflozin vs. placebo. OUTCOMES MEASURED: All-cause mortality, defined as death of patient within the study interval and expressed as number of death/ total participants over the study time interval. RESULTS: The search yielded a total of 20 articles. Three studies were ultimately included in the EBM review after exclusion of other irrelevant studies. Neal et al. showed no statistically significant reduction in all-cause mortality rate, 17.3 vs. 19.5 participants with an event per 1000 patient-years between the intervention vs. placebo groups, respectively (HR 0.87; 95% CI 0.74 to 1.01; P = 0.24). In the Perkovic study, all-cause mortality rate was also similar between both groups, 29.0 vs. 35.0 per 1000 patient-years (HR 0.83; 95% CI 0.68–1.02; P not given) for the intervention and placebo groups, respectively. Likewise, all-cause mortality rate was shown to be the same, 1.1 % in both the placebo and the treatment arms in Yale et al. study. CONCLUSIONS: The results of all three studies demonstrated that canagliflozin is not effective in lowering the risk of all-cause mortality in adults with type 2 diabetes compared to the matched placebo. Due to the potential heterogeneity among the included studies, the results of this analysis should be confirmed with new and larger trials in the future to better evaluate all-cause mortality over a longer follow-up period