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The increased risk of amputation seen in the large, long-term Canagliflozin Cardiovascular Assessment Study (CANVAS) trial for canagliflozin, and select observational studies, merits further research but overall, there is currently no consistent evidence of SGLT2i exposure and increased risk of amputation

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The environment can also alter DNA methylation or histone modifications, regulating the expression of inflammatory genes and enhancing the innate immune response ( Figure 2 )

But that still does not guarantee that the real-world performance will match the label exactly