The moderate number of events for vital renal outcomes limits the interpretations about effects on kidney failure.
Differences in effect sizes could be attributed to trial design or chance since the precision in effect estimates is limited.
Greater use of other glucose-lowering agents in the placebo group could have underestimated any real benefits and risks.
Increased rate of amputation with an unknown mechanism necessitates caution in using canagliflozin in patients at risk for amputation.
The relative risk of amputation varied across subgroups based on history and risk of peripheral vascular disease.

FundingSupported by Janssen Research and Development.Further ReadingFull text details available in the New England Journal of Medicine, published on June 12, 2017.