Treating Diabetis with Metformin

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Canagliflozin (Invokana®)

Canagliflozin (Invokana®) is a new antihyperglycemic agent approved in March 2013 for the treatment of type 2 diabetes. Canagliflozin was the first sodium-glucose co-transporter 2 (SGLT2) inhibitor to be approved by the FDA.1 Based on the 2014 ADA guideline Metformin is the preferred initial therapy (if tolerated and not contraindicated), and insulin therapy with or without other agents should be considered in newly diagnosed patients with markedly symptomatic and/or elevated blood glucose levels or A1C. If noninsulin monotherapy at maximal tolerated dose does not achieve or maintain A1C target over 3 month, a 2nd oral agent (Sulfonylurea, TZDs, and DPP-4), GLP-1 receptor agonist, or insulin should be added.2

Pharmacology:2 By inhibiting SGLT2, canagliflozin reduces the renal threshold for glucose and increases urinary glucose excretion by interfering with the reabsorption of glucose across the proximal renal tubules.

Pharmacokinetics:2 oral bioavailability of canagliflozin is approximately 65. Reach Tmax after 1 to 2 hours, reaches steady state in 4 to 5 hrs. Canagliflozin is 99% protein bound. Eliminated trough renal route 33% (primarily metabolites) and fecal (41.5%).

Dose: 2 Starting dose of canagliflozin is 100 mg PO once daily before the first meal of the day. If patient tolerates 100mg daily and has an eGFR of 60 mL/min/1.73 m2 or greater, the dose can be titrated to 300mg daily.
Dose adjustment (renal impairment): In patients with an eGFR of 45 to 60 mL/min/1.73 m2, the dose of canagliflozin is limited to 100 mg once daily, Canagliflozin should not be used in patients with an eGFR less than 45 mL/min/1.73 m2.

Contraindications: 2 hypersensitivity to canagliflozin. Sever renal impairment, (...

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...5. Stenlöf, K., Cefalu, W. T., Kim, K. A., Alba, M., Usiskin, K., Tong, C., ... & Meininger, G. (2013). Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes, Obesity and Metabolism.
6. Cefalu, W. T., Leiter, L. A., Yoon, K. H., Arias, P., Niskanen, L., Xie, J., ... & Meininger, G. (2013). Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. The Lancet, 382(9896), 941-950.
7. Schernthaner G, Gross JL, Rosenstock J, et al. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycaemic control with metformin plus a sulfonylurea. Diabetes Care. 2013. doi

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