Invokana(canagliflozin)

Invokana (canagliflozin) is a medication initially approved in the U.S. on March 29, 2013. It has demonstrated effectiveness in reducing the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure. It is also effective in slowing the loss of kidney function and delaying progression to ESKD and reducing CV death. In clinical trials, canagliflozin showed a reduction in the composite endpoint of CV death and hospitalization for heart failure (HR 0.69, P-value 0.0001) and a reduction in the renal composite endpoint (ESKD, doubling of serum creatinine, and renal death) (HR 0.66, P-value <0.0001). It also reduced MACE (non-fatal MI, non-fatal stroke, and CV death) (HR 0.80, P-value 0.012) and hospitalization for heart failure (HR 0.61, P-value 0.0003).

Regarding glycemic control, canagliflozin resulted in an HbA1C change from baseline of -1.03% and -0.91% vs placebo. Approximately 47% of patients achieved HbA1C < 7%. The drug was studied in a randomized, double-blind, parallel-group, event-driven trial with placebo as a comparator, typically at a dosage of 100 mg once daily.

Safety findings include a higher rate of lower limb amputations in the canagliflozin arm (12.3 events per 1000 patient years) compared to placebo (11.2 events per 1000 patient years). The rate of adjudicated events of diabetic ketoacidosis was 0.21 per 100 patient-years of follow-up in the canagliflozin arm, compared to 0.03 per 100 patient-years in the placebo arm. The incidence of hypotension was 2.8% in the canagliflozin arm versus 1.5% in the placebo arm. The incidence of acute kidney injury was 3.9% in the canagliflozin arm compared to 4.5% in the placebo arm.