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Canagliflozin did not statistically significantly increase the risk for lower-limb amputations, fractures, acute kidney in- jury, or hyperkalemia but did increase the risk for diabetic ketoacidosis (2.2 and 0.2 events per 1000 patient-years in the canagliflozin and placebo groups, respectively)

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Piperine also inhibited monoamine oxidase (MAO) activity, and increased the levels of noradrenaline and serotonin in some regions of the mouse brain