Incretin strategy in the treatment of type 2 diabetes mellitus – the DPP-IV inhibitor sitagliptin

Czech version

Authors: J. Perušičová
Authors‘ workplace: Diabetologické centrum Interní kliniky 2. lékařské fakulty UK a FN Motol Praha, přednosta prof. MUDr. Milan Kvapil, CSc.
Published in: Vnitř Lék 2007; 53(10): 1109-1113
Category: Reviews

Overview

Sitagliptin, distributed under the brand name of Januvia, has been the first and so far the only dipeptidyl peptidase IV (DPP-IV) inhibitor introduced in clinical practice. The results of published clinical studies clearly demonstrate its effectiveness and safety as an oral antidiabetic. Apart from increasing the insulin level, Sitagliptin reduces the level of glucagon. The principal advantages of Sitagliptin from the clinical point of view are: a) the ability to reduce both fasting and non-fasting glycaemia and improve the HbA1c values, b) the fact that it does not provoke weight increase, c) the fact that the risk of hypoglycaemia is significantly lower as compared with sulfonylurea derivatives, d) good tolerability.

Keywords:
DPP-IV – Sitagliptin – type 2 diabetes mellitus

Sources

1. Aschner P, Kipnes MS, Lunceford JK et al. for Sitagliptin Study 021 Group: Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy onglycemic control in patients with type 2 diabetes. Diabetes Care 2006; 29: 2632-2637.

2. Bergman AJ, Stevens C, Zhou Y et al. Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: a double-blind, randomized, placebo-controlled study in healthy male volunteers. Clin Ther 2006; 28: 55-72.

3. Charbonnel B, Karasik A, Liu J et al. for Sitagliptin Study 020 Group: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin addedto ongoing metformin therapy in patients with type 2 diabetes inadequatelycontrolled with metformin alone. Diabetes Care 2006; 29: 2638-2643.

4. Conarello SL, Li Z, Shelton B et al. Dipeptidyl peptidase knockout mice are protected against high fat diet-induced obesity and insulin resistance. Am Diabetes Assoc, 62nd Scientific Sessions, 2002 San Francisco, California

5. Deacon CF. Dipeptidyl peptidase 4 inhibition with sitagliptin: a new therapy for type 2 diabetes. Expert Opin Investig Drugs 2007; 16: 533-545.

6. Deacon CF, Ahrén B, Holst JJ. Inhibitors of dipeptidyl peptidase IV: a novel approach for the prevention and treatment of type 2 diabetes? Expert Opin Investig Drugs 2004; 13: 1091-1102.

7. Herman GA, Bergman A, Yi B, Kipnes M et al. for The Sitagliptin Study 012 Group: Tolerability and pharmacokinetics of metformin and the dipeptidyl peptidase-4 inhibitor sitagliptin when co-administered in patients with type 2 diabetes. Curr Med Res Opin 2006; 22: 1939-1947.

8. Herman GA, Hergman A, Stevens C et al. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test inpatients with type 2 diabetes. J Clin Endocrinol Metab 2006; 91: 4612-4619.

9. Herman GA, Stevens C, Van Dyck K et al. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther 2005; 78: 675-688.

10. Hermansen K, Kipnes M, Luo E et al. Efficacy and safety of 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(5): 733-745.

11. Hunziker D, Hennig M, Peters JU. Inhibitors of Dipeptidyl Peptidase IV - Recent Advances and Structural Views. Curr Top Med Chem 2005; 5: 1623-1637.

12. Lyseng-Wiliamson KA Sitagliptin. Drugs 2007; 67: 587-597.

13. Mannucci E, Ognibene A, Cremasco F et al. Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese non-diabetic subjects. Diabetes Care 2001; 24: 489-494.

14. Miller S, St Onge EL. Sitagliptin: a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Ann Pharmacother 2006; 40: 1336-1343.

15. Mu J, Woods J et al. Chronic Inhibition of dipeptidyl peptidase-4 with a sitagliptin analog preserves pancreatic beta-cell mass and function in a rodent model of type 2 diabetes. Diabetes 2006; 55: 1695-1704.

16. Nauck MA, Meininger G, Sheng D et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with sulphonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double blind, non-inferiority trial. Diabetes Obes Metab 2007; 9: 194-205.

17. Pratley RE, Salsali A. Inhibitors of Dipeptidyl Peptidase IV - A new therapeutic approach for the treatment of type 2 diabetes. Curr Med Res Opin 2007; 23: 919-931.

18. Raz I, Hanefeld M, Xu L et al. for Sitagliptin Study 023 Group: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia 2006; 49: 2564-2571.

19. Rosenstock J, Brazg R, Andryuk PJ et al. for Sitagliptin Study 019 Group: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther 2006; 28: 1556-1568.

20. Schirra J, Sturm K, Leicht P et al. Exendin (9-39) is an antagonist of glucagon-like peptide-1 (7-36) amide in humans. J Clin Invest 1998; 101: 1421-1430.

21. Scott R, Wu M, Sanchez M et al. Efficacy and tolerability of the dipeptidyl peptidase-4 inhibition sitagliptin as monotherapy over 12 weeks in patients with type 2 diabetes. Int J Clin Pract 2006; 61: 171-180.

22. Vincent SH, Reed JR, Bergman AJ et al. Metabolism and excretion of the dipeptidy peptidase 4 inhibition (14C) sitagliptin in humans. Drug Meab Dispos 2007; 35: 533-538.

23. Yang J, Campitelli J, Hu G et al. Increase in DPP-IV in intestine, liver and kidney of the rat treated with fat diet and streptozotocin. Life Sci 2007; 81: 272-279.