Efficacy and safety of canagliflozin in Japanese patients with type 2 diabetes: a randomized, double‐blind, placebo‐controlled, 12‐week study

Abstract

Aims We examined the efficacy, safety and tolerability of canagliflozin, a sodium glucose co‐transporter 2 inhibitor, in Japanese patients with type 2 diabetes ( T2DM ) undergoing diet and exercise therapy. Methods Patients aged 20–80 years with T2DM diagnosed ≥3 months previously, and HbA1c of 6.9–9.9% were randomized to 50, 100, 200 or 300 mg canagliflozin or placebo once daily for 12 weeks. The primary and secondary endpoints were changes in HbA1c , fasting plasma glucose ( FPG ), urinary glucose/creatinine and postprandial glycaemic parameters following a meal test. The safety assessments included adverse events ( AEs ) and clinical laboratory tests. Results Overall, 383 patients were randomized to receive either placebo (n = 75), or 50 mg (n = 82), 100 mg (n = 74), 200 mg (n = 77) or 300 mg canagliflozin (n = 75). At week 12, significant reductions in HbA1c were observed in all canagliflozin groups relative to placebo (−0.61, –0.80, –0.79 and −0.88% for 50, 100, 200 and 300 mg, respectively, versus +0.11% for placebo; all, p < 0.01). FPG and postprandial glycaemic parameters improved significantly in the canagliflozin groups. Body weight was significantly decreased by canagliflozin. No deaths or drug‐related serious AEs were reported. There was no dose‐dependent increase in the incidence of AEs in the canagliflozin groups. The incidence of hypoglycaemia was low; episodes were not severe or dose dependent. Canagliflozin did not affect serum creatinine levels or the urinary albumin/creatinine ratio. Conclusions Treatment with canagliflozin for 12 weeks significantly improved glycaemic control and reduced body weight in Japanese patients with T2DM . Canagliflozin was well tolerated.

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References 23

1. 1.

   IDF Diabetes Atlas. 2011.

   Not in our library

2. 2.

   Standards of medical care in diabetes--2012. Diabetes Care. 2012;35(Suppl 1):S11-63.

   Not in our library10.2337/dc12-s011

3. 3.

   Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193-203.

   Not in our library10.2337/dc08-9025

4. 4.

   Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427-2443.

   Not in our library10.1056/nejmoa066224

5. 5.

   Rave K, Nosek L, Posner J, Heise T, Roggen K, van Hoogdalem EJ. Renal glucose excretion as a function of blood glucose concentration in subjects with type 2 diabetes--results of a hyperglycaemic glucose clamp study. Nephrol Dial Transplant. 2006;21:2166-2171.

   Not in our library10.1093/ndt/gfl175

6. 6.

   Ruhnau B, Faber OK, Borch-Johnsen K, Thorsteinsson B. Renal threshold for glucose in non-insulin-dependent diabetic patients. Diabetes Res Clin Pract. 1997;36:27-33.

   Not in our library10.1016/s0168-8227(97)01389-2

7. 7.

   Nair S, Wilding JP. Sodium glucose cotransporter 2 inhibitors as a new treatment for diabetes mellitus. J Clin Endocrinol Metab. 2010;95:34-42.

   Not in our library10.1210/jc.2009-0473

8. 8.

   Rahmoune H, Thompson PW, Ward JM, Smith CD, Hong G, Brown J. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes. 2005;54:3427-3434.

   Not in our library10.2337/diabetes.54.12.3427

9. 9.

   Abdul-Ghani MA, DeFronzo RA. Inhibition of renal glucose reabsorption: a novel strategy for achieving glucose control in type 2 diabetes mellitus. Endocr Pract. 2008;14:782-790.

   Not in our library10.4158/ep.14.6.782

10. 10.

    Chen LH, Leung PS. Inhibition of the sodium glucose co-transporter-2: its beneficial action and potential combination therapy for type 2 diabetes mellitus. Diabetes Obes Metab. 2013;15:392-402.

    Not in our library10.1111/dom.12064

11. 11.

    DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab. 2012;14:5-14.

    Not in our library10.1111/j.1463-1326.2011.01511.x

12. 12.

    Nomura S, Sakamaki S, Hongu M, et al. Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus. J Med Chem. 2010;53:6355-6360.

    Not in our library10.1021/jm100332n

13. 13.

    Sha S, Devineni D, Ghosh A, et al. Canagliflozin, a novel inhibitor of sodium glucose co-transporter 2, dose dependently reduces calculated renal threshold for glucose excretion and increases urinary glucose excretion in healthy subjects. Diabetes Obes Metab. 2011;13:669-672.

    Not in our library10.1111/j.1463-1326.2011.01406.x

14. 14.

    Devineni D, Morrow L, Hompesch M, et al. Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin. Diabetes Obes Metab. 2012;14:539-545.

    Not in our library10.1111/j.1463-1326.2012.01558.x

15. 15.

    Rosenstock J, Aggarwal N, Polidori D, et al. Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes. Diabetes Care. 2012;35:1232-1238.

    Not in our library10.2337/dc11-1926

16. 16.
    Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise · 2013

    No notice
17. 17.

    List JF, Woo V, Morales E, Tang W, Fiedorek FT. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care. 2009;32:650-657.

    Not in our library10.2337/dc08-1863

18. 18.

    Wilding JP, Norwood P, T’Joen C, Bastien A, List JF, Fiedorek FT. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment. Diabetes Care. 2009;32:1656-1662.

    Not in our library10.2337/dc09-0517

19. 19.

    Kaku K, Inoue S, Matsuoka O, et al. Efficacy and safety of dapagliflozin as a monotherapy for type 2 diabetes mellitus in Japanese patients with inadequate glycaemic control: a phase II multicentre, randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2013;15:432-440.

    Not in our library10.1111/dom.12047

20. 20.

    Polidori D, Sha S, Devineni D, Rothenberg P. 2010.

    Not in our library

21. 21.

    Liang Y, Du F, Conway JG, Polidori D, Clapper J, Demarest K. 2011.

    Not in our library

22. 22.

    Polidori D, Sakai M, Devineni D. 2011.

    Not in our library

23. 23.

    Jurczak MJ, Lee HY, Birkenfeld AL, et al. SGLT2 deletion improves glucose homeostasis and preserves pancreatic beta-cell function. Diabetes. 2011;60:890-898.

    Not in our library10.2337/db10-1328

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