Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease

Abstract

Aims Canagliflozin is a sodium glucose co‐transporter 2 inhibitor in development for treatment of type 2 diabetes mellitus ( T2DM ). This study evaluated the efficacy and safety of canagliflozin in subjects with T2DM and stage 3 chronic kidney disease [ CKD ; estimated glomerular filtration rate ( eGFR ) ≥30 and <50 ml /min/1.73 m 2 ]. Methods In this randomized, double‐blind, placebo‐controlled, phase 3 trial, subjects (N = 269) received canagliflozin 100 or 300 mg or placebo daily. The primary efficacy endpoint was change from baseline in HbA1c at week 26. Prespecified secondary endpoints were change in fasting plasma glucose ( FPG ) and proportion of subjects reaching HbA1c <7.0%. Safety was assessed based on adverse event ( AE ) reports; renal safety parameters (e.g. eGFR , blood urea nitrogen and albumin/creatinine ratio) were also evaluated. Results Both canagliflozin 100 and 300 mg reduced HbA1c from baseline compared with placebo at week 26 (–0.33, –0.44 and –0.03%; p < 0.05). Numerical reductions in FPG and higher proportions of subjects reaching HbA1c < 7.0% were observed with canagliflozin 100 and 300 mg versus placebo (27.3, 32.6 and 17.2%). Overall AE rates were similar for canagliflozin 100 and 300 mg and placebo (78.9, 74.2 and 74.4%). Slightly higher rates of urinary tract infections and AEs related to osmotic diuresis and reduced intravascular volume were observed with canagliflozin 300 mg compared with other groups. Transient changes in renal function parameters that trended towards baseline over 26 weeks were observed with canagliflozin. Conclusion Canagliflozin improved glycaemic control and was generally well tolerated in subjects with T2DM and Stage 3 CKD .

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References 26

1. 1.

   Kramer H, Molitch ME. Screening for kidney disease in adults with diabetes. Diabetes Care. 2005;28:1813-1816.

   Not in our library10.2337/diacare.28.7.1813

2. 2.

   Flynn C, Bakris G. Noninsulin glucose-lowering agents for the treatment of patients on dialysis. Nat Rev Nephrol. 2013;9:147-153.

   Not in our library10.1038/nrneph.2013.12

3. 3.

   Cavanaugh KL. Diabetes management issues for patients with chronic kidney disease. Clin Diabetes. 2007;25:90-97.

   Not in our library

4. 4.

   Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35:1364-1379.

   Not in our library10.2337/dc12-0413

5. 5.

   Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-853.

   Not in our library

6. 6.

   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

7. 7.

   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

8. 8.
   Effect of Canagliflozin on Renal Threshold for Glucose, Glycemia, and Body Weight in Normal and Diabetic Animal Models · 2012

   No notice
9. 9.

   Devineni D, Morrow L, Hompesch M, et al. Canagliflozin improves glycemic 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

10. 10.

    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

11. 11.

    Polidori D, Sakai M, Devineni D. Exposure-response modeling of canagliflozin effects on the renal glucose threshold in subjects with type 2 diabetes (T2DM) (Abstract 1072-P). Diabetes. 2011;60(Suppl. 1):A294.

    Not in our library

12. 12.

    Levey AS, Coresh J, Greene T, et al. Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem. 2007;53:766-772.

    Not in our library10.1373/clinchem.2006.077180

13. 13.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1542/peds.111.6.1416

14. 14.

    Niskanen L, Cefalu WT, Leiter LA, et al. Efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, compared with glimepiride in patients with type 2 diabetes on background metformin (Abstract 763). Diabetologia. 2012;55(Suppl. 1):S314.

    Not in our library

15. 15.

    Schernthaner G, Gross J, Fu M, et al. Efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, compared with sitagliptin in patients with type 2 diabetes on metformin plus sulphonylurea (Abstract 243). Diabetologia. 2012;55(Suppl. 1):S108.

    Not in our library

16. 16.

    Stenlof K, Cefalu WT, Tong C, et al. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves glycaemic control in subjects with type 2 diabetes inadequately controlled with diet and exercise (Abstract 760). Diabetologia. 2012;55(Suppl. 1):S312-313.

    Not in our library

17. 17.

    Wilding J, Mathieu C, Deng L, et al. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves glycaemia in subjects with type 2 diabetes inadequately controlled with metformin plus sulphonylurea (Abstract 766). Diabetologia. 2012;55(Suppl. 1):S315-316.

    Not in our library

18. 18.

    Devineni D, Marbury TC, Curtin CR, et al. Effects of renal function on canagliflozin (CANA) pharmacokinetics (PK) and pharmacodynamics (PD) in non-diabetic subjects (Abstract PUB295). J Am Soc Nephrol. 2012;23:961A.

    Not in our library

19. 19.

    Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004;27:2628-2635.

    Not in our library10.2337/diacare.27.11.2628

20. 20.

    Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab. 2007;9:733-745.

    Not in our library10.1111/j.1463-1326.2007.00744.x

21. 21.

    Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005;28:1083-1091.

    Not in our library10.2337/diacare.28.5.1083

22. 22.

    Strojek K, Yoon KH, Hruba V, Elze M, Langkilde AM, Parikh S. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2011;13:928-938.

    Not in our library10.1111/j.1463-1326.2011.01434.x

23. 23.

    Wilding JP, Woo V, Soler NG, et al. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med. 2012;156:405-415.

    Not in our library10.7326/0003-4819-156-6-201203200-00003

24. 24.

    de Zeeuw D, Remuzzi G, Parving HH, et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int. 2004;65:2309-2320.

    Not in our library10.1111/j.1523-1755.2004.00653.x

25. 25.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

26. 26.

    Kohan DE, Fioretto P, List J, Tang W. Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (Abstract TH-PO524). J Am Soc Nephrol. 2011;22(Suppl):232-A.

    Not in our library

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