SAXAGLIPTIN OPENS NEW OPPORTUNITIES FOR EFFECTIVE AND SAFE GLYCEMIC CONTROL IN PATIENTS WITH TYPE 2 DIABETES MELLITUS


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Abstract

Modern pharmacotherapy of type 2 diabetes mellitus (DM2) should be directed not only at reducing the level of glycated hemoglobin, fasting plasma glucose and postprandial glycemia, but also at all components of pathogenesis of the disease. Violation of incretine's secretion is one of the important mechanisms for the development of hyperglycemia in type 2 diabetes mellitus. Incretines are hormones acting on β- and α-cells of the pancreas, increasing insulin secretion and suppressing glucagon secretion, thereby maintaining normoglycemia. The dipeptylpeptidase type IV (DPP-4) is enzyme inactivating incretines. DPP-4 inhibitors are used in the treatment of type 2 diabetes mellitus. The article presents the results of clinical trials of a new DPP-4 inhibitor saxagliptin. These clinical studies have confirmed the efficacy and safety of saxagliptin in patients with type 2 diabetes mellitus both as monotherapy and in combination with other oral hypoglycemic agents.

References

  1. Deacon CF, Carr RD, Holst JJ. DPP-4 inhibitor therapy: new directions in the treatment of type 2 diabetes. Front Biosci 2008;13:1780-94.
  2. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007;132:2131-57.
  3. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev 2007;87:1409-39.
  4. Holst JJ, Vilsboll T, Deacon CF. The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol 2009;297:127-36.
  5. Vilsboll T, Holst JJ. Incretins, insulin secretion and type 2 diabetes mellitus. Diabetologia 2004;47:357-66.
  6. Zander M, Madsbad S, Madsen JL, et al. Effect of 6-week course of glucagon-like peptide 1 on gly-caemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 2002;359:824-30.
  7. Augeri DJ, Robl JA, Betebenner DA, et al. Discovery and preclinical profile of saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem 2005;48:5025-37.
  8. Kim YB, Kopcho LM, Kirby MS, et al. Mechanism of Gly-Pro-pNA cleavage catalyzed by dipeptidyl peptidase-IV and its inhibition by saxagliptin (BMS-477118). Arch Biochem Biophys 2006;445:9-18.
  9. Boulton DW, Goyal A, Li L, et al. The effects of age and gender on the single-dose pharmacokinetics and safety of saxagliptin in healthy subjects [abstract no. 551-P]. Diabetes 2008;57(1): A164.
  10. Boulton D, Tang A, Patel C, et al. Pharmacokinetics of dipeptidyl pepetidase-4 inhibitor saxagliptin in subjects with renal impairment [abstract no. P357]. 11th European Congress of Endocrinology 2009:25-9.
  11. Patel C, Castaneda L, Frevert U, et al. Single-dose pharmacokinetics and safety of saxagliptin in subjects with hepatic impairment compared with healthy subjects [abstract no. 537-P]. Diabetes 2008;57(1):A160.
  12. Rosenstock J, Sankoh S, List JF. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab 2008;10(5):376-86.
  13. Rosenstock J, Aguilar-Salinas CA, Klein E, et al. Once-daily saxagliptin monotherapy improves glycaemic control in drug-naive patients with type 2 diabetes [abstract]. Diabetes 2008;57(1):A154.
  14. Jadzinsky M, Pfutzner A, Paz-Pacheco E, et al. Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diabetes Obes Metab 2009;11(6):611-22.
  15. DeFronzo RA, Hissa MN, Garber AJ, et al. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes on metformin alone. Diabetes Care 2009;32(9):1649-55.
  16. Chacra AR, Tan GH, Apanovitch A, et al. Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonyl-urea in patients with type 2 diabetes: a randomised controlled trial. Int J Clin Pract 2009;63(9):1395-406.
  17. Ravichandran S, Chacra AR, Tan GH, et al. Saxagliptin added to a sub-maximal-dose sulfonylurea is safe and more efficacious than up-titrating a sulfonylurea in patients with type 2 diabetes [abstract]. Diabetologia 2008;51(1):S342.
  18. Hollander P, Allen E, Li J, et al. Saxagliptin added to a thiazolidinedione improves glycemic control in patients with inadequately controlled type 2 diabetes [abstract]. Diabetologia 2008;51(1):S342.
  19. Wolf R, Frederich R, Fiedorek F, et al. Evaluation of CV risk in saxagliptin clinical trials [abstract no. 8-LB plus poster]. 69th Annual Scientific Sessions of the American Diabetes Association 2009:5-9.

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