s.
Company
Janssen Pharmaceuticals, Inc.
Indication(s):
Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). Limitation of use: not for treatment of type 1 diabetes or diabetic ketoacidosis.
Pharmacology:
Canagliflozin inhibits the sodium-glucose co-transporter 2, which reduces reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.
Clinical Trials:
Canagliflozin has been studied as monotherapy, in combination with metformin, sulfonylurea, metformin and sulfonylurea, metformin and a thiazolidinedione (eg, pioglitazone), and in combination with insulin (with or without other antihyperglycemic agents). The efficacy of canagliflozin was compared to a dipeptidyl peptidase‑4 (DPP‑4) inhibitor (sitagliptin) and a sulfonylurea (glimepiride). Canagliflozin was also eva luated in adults 55–80 years of age and patients with moderate renal impairment. In patients with T2DM, treatment with canagliflozin produced clinically and statistically significant improvements in HbA1c compared to placebo.
A total of 584 patients with T2DM inadequately controlled on diet and exercise participated in a 26‑week, double-blind, placebo-controlled study to eva luate the efficacy and safety of canagliflozin monotherapy. Patients taking other antihyperglycemic agents (N=281) discontinued the agent and underwent an 8-week washout followed by a 2‑week, single-blind, placebo run-in period. Patients not taking oral antihyperglycemic agents (N=303) entered the 2‑week, single-blind, placebo run-in period directly. After the placebo run-in period, patients were randomized to canagliflozin 100mg, canagliflozin 300mg, or placebo, given once daily for 26 weeks. At the end of treatment, both canagliflozin doses resulted in a statistically significant improvement in HbA1c (P <0.001 for both doses) vs. placebo. Also, both doses resulted in a greater proportion of patients achieving an HbA1c <7%, in significant reduction in fasting plasma glucose, in improved postprandial glucose, and in percent body weight reduction compared to placebo. Statistically significant (P <0.001 for both doses) mean changes from baseline in systolic BP relative to placebo were ‑3.7 mmHg and ‑5.4 mmHg with canagliflozin 100mg and 300mg, respectively.
For information on studies conducted in add-on combination therapy and in special populations: see full labeling.
Legal Classification:
Rx
Adults:
See full labeling. Take before first meal of the day. Initially 100mg once daily; if tolerated and with eGFR ≥60mL/min/1.73m2, and need additional glycemic control; may increase to 300mg once daily. Moderate renal impairment (eGFR 45–<60mL/min/1.73m2): 100mg once daily; if eGFR <45mL/min/1.73m2: do not initiate. Concomitant UGT inducers in patients with eGFR ≥60mL/min/1.73m2: consider increase to 300mg once daily; if eGFR 45–<60mL/min/1.73m2: consider other antihyperglycemics.
Children:
<18 years: not established.
Contraindication(s):
Severe renal impairment (eGFR <30mL/min/1.73m2), ESRD, or patients on dialysis.
Warnings/Precautions:
Correct volume depletion before starting therapy. Monitor for symptomatic hypotension in patients with renal impairment (eGFR <30mL/min/1.73m2), elderly, |
