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Vildagliptin

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Abstract

  • ▴ Vildagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that is being evaluated in the treatment of patients with type 2 diabetes mellitus. It improves glycaemic control by inhibiting DPP-4 from inactivating the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, prolonging incretin activity in response to ingestion of nutrients. This allows for increased insulin sensitivity, decreased glucagon secretion and improved β-cell function in a glucose-dependent manner.

  • ▴ Glycaemic control with vildagliptin 50 or 100 mg/day, measured by a change from baseline in mean glycosylated haemoglobin (HbA1c) at study endpoint, was improved relative to placebo in several well designed clinical trials of vildagliptin monotherapy in patients with type 2 diabetes. In randomised active comparator studies, noninferiority of vildagliptin in reducing HbA1c levels from baseline was established to rosiglitazone, but not to metformin.

  • ▴ Vildagliptin also showed efficacy in reducing HbA1c levels in patients with type 2 diabetes when used in combination with metformin, pioglitazone or insulin.

  • ▴ Vildagliptin was generally well tolerated when administered alone or in combination with additional antidiabetic treatment. Gastrointestinal adverse events were mild to moderate in intensity, and occurred less frequently than with metformin. Hypoglycaemic events were rare and occurred at a similar incidence to that with placebo.

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Notes

  1. The use of trade names is for identification purposes only and does not imply endorsement.

References

  1. Diagnosis and classification of diabetes mellitus. Diabetes Care 2006 Jan; 29 Suppl. 1: S43-7

  2. Standards of medical care in diabetes: 2006. Diabetes Care 2006 Jan; 29 Suppl. 1: S4-42

  3. Gallwitz B. Glucagon-like peptide-1-based therapies for the treatment of type 2 diabetes mellitus. Treat Endocrinol 2005; 4(6): 361–70

    Article  PubMed  CAS  Google Scholar 

  4. Nielsen LL. Incretin mimetics and DPP-IV inhibitors for the treatment of type 2 diabetes. Drug Discov Today 2005; 10(10): 703–10

    Article  PubMed  CAS  Google Scholar 

  5. Ahren B, Schmitz O. GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes. Horm Metab Res 2004; 36(11–12): 867–76

    Article  PubMed  CAS  Google Scholar 

  6. Demuth HU, McIntosh CH, Pederson RA. Type 2 diabetes: therapy with dipeptidyl peptidase IV inhibitors. Biochim Biophys Acta 2005 Aug 1; 1751(1): 33–44

    Article  PubMed  CAS  Google Scholar 

  7. Mentlein R. Therapeutic assessment of glucagon-like peptide-1 agonists compared with dipeptidyl peptidase IV inhibitors as potential antidiabetic drugs. Expert Opin Investig Drugs 2005 Jan; 14(1): 57–64

    Article  PubMed  CAS  Google Scholar 

  8. Deacon CF, Holst JJ. Dipeptidyl peptidase IV inhibitors: a promising new therapeutic approach for the management of type 2 diabetes. Int J Biochem Cell Biol 2006; 38(5–6): 831–44

    Google Scholar 

  9. Ahren B, Gomis R, Standl E, et al. Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care 2004 Dec; 27(12): 2874–80

    Article  PubMed  CAS  Google Scholar 

  10. Rosenstock J, Baron MA, Schweizer A, et al. Vildagliptin is as effective as rosiglitazone in lowering HbA1c but without weight gain in drug-naive patients with type 2 diabetes (T2DM) [abstract no. 557-P]. Diabetes 2006; 55 Suppl. 1: A 133. Plus poster presented at the American Diabetes Association 66th Scientific Sessions; 2006 Jun 9–13; Washington, DC

    Google Scholar 

  11. Ahren B, Pacini G, Foley JE, et al. Improved meal-related beta-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year. Diabetes Care 2005 Aug; 28(8): 1936–40

    Article  PubMed  CAS  Google Scholar 

  12. Pratley RE, Jauffret-Kamel S, Galbreath E, et al. Twelve-week monotherapy with the DPP-4 inhibitor vildagliptin improves glycemic control in subjects with type 2 diabetes. Horm Metab Res 2006 Jun; 38(6): 423–8

    Article  PubMed  CAS  Google Scholar 

  13. Ristic S, Byiers S, Foley J, et al. Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response. Diabetes Obes Metab 2005 Nov; 7(6): 692–8

    Article  PubMed  CAS  Google Scholar 

  14. He YL, Balch A, Campestrini J, et al. Pharmacokinetics and pharmacodynamics of the DPP-4 inhibitor, LAF237, in patients with type 2 diabetes. Clin Pharmacol Ther 2005 Feb; 77(2): 56

    Google Scholar 

  15. Matikainen N, Manttari S, Schweizer A, et al. Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes. Diabetologia 2006 Jul 1;49: 2049–57

    Article  PubMed  CAS  Google Scholar 

  16. Mari A, Sallas WM, He YL, et al. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab 2005 Aug; 90(8): 4888–94

    Article  PubMed  CAS  Google Scholar 

  17. He YL, Horowitz A, Watson C, et al. Lack of effect of LAF237 on C-peptide clearance in patients with type 2 diabetes. Clin Pharmacol Ther 2005 Feb; 77(2): 56

    Google Scholar 

  18. Ahren B, Landin-Olsson M, Jansson PA, et al. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab 2004 May; 89(5): 2078–84

    Article  PubMed  CAS  Google Scholar 

  19. D’Alessio DA, Watson CE, He Y-L, et al. Restoration of an acute insulin response to glucose (AIRg) in drug-naive patients with type 2 diabetes (T2DM) by 3-month treatment with vildagliptin [abstract no. 454-P]. Diabetes 2006 Jun; 55 Suppl. 1: A108

    Google Scholar 

  20. Azuma K, Radikova Z, Mancino JM, et al. DPP-4 inhibition improves insulin resistance (IR) in type 2 DM [abstract no. 5-LB]. American Diabetes Association 66th Scientific Sessions; 2006 Jun 9–13; Washington, DC

  21. Balas B, Baig M, Watson C, et al. Vildagliptin suppresses endogenous glucose production (EGP) and increases beta cell function after single dose administration in type 2 diabetic (T2D) patients [abstract no. 122-OR]. Diabetes 2006 Jun; 55 Suppl. 1: A29

    Google Scholar 

  22. Vella A, Bock MD, Giesler PD, et al. The effect of the dipeptidyl peptidase IV inhibitor LAF237 on gastrointestinal function and glucose metabolism in type 2 diabetes. American Diabetes Association 66th Scientific Sessions; 2006 Jun 9–13; Washington, DC

  23. Kelley DE, Dunning BE, Ligueros-Saylan M, et al. Four-week treatment with vildagliptin increases fasting plasma levels of intact incretin hormones both in patients with type 1 (T1DM) and type 2 (T2DM) diabetes [abstract no. 1481-P]. Diabetes 2006 Jun; 55 Suppl. 1: A344

    Google Scholar 

  24. Shannon J. Key Late Stage Projects (Investor presentation) [online]. Available from URL: http://www.novartis.com/ [Accessed 2006 Jul 20]

  25. Villhauer EB, Brinkman JA, Naderi GB, et al. l-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J Med Chem 2003; 46: 2774–89

    Article  PubMed  CAS  Google Scholar 

  26. Brandt I, Joossens J, Chen X, et al. Inhibition of dipeptidyl-peptidase IV catalyzed peptide truncation by vildagliptin ((2S)- [(3-hydroxyadamantan-1-yl)amino]acetyl-pyrrolid ine-2-carbonitrile). Biochem Pharmacol 2005 Jul 1; 70(1): 134–43

    Article  PubMed  CAS  Google Scholar 

  27. Hughes TE, Mone MD, Russell ME, et al. NVP-DPP728 (1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)- pyrrolidine), a slow-binding inhibitor of dipeptidyl peptidase IV. Biochemistry (Mosc) 1999; 38: 11597–603

    Article  CAS  Google Scholar 

  28. He Y-LL, Sabo R, Wang Y, et al. The influence of hepatic impairment on the pharmacokinetics of vildagliptin [abstract no. 2024-PO]. Diabetes 2006 Jun; 55 Suppl. 1: A4469

    Google Scholar 

  29. He YL, Sabo R, Balez S, et al. Absolute bioavailability of vildagliptin in healthy subjects. Clin Pharmacol Ther 2006 Feb; 79(2): 38

    Article  Google Scholar 

  30. He YL, Sabo R, Wang Y, et al. The influence of age, gender and BMI on the pharmacokinetics and pharmacodynamics of vildagliptin. Clin Pharmacol Ther 2006 Feb 1; 79(2): 63

    Article  Google Scholar 

  31. Barilla D, He Y, Balez S, et al. No pharmacokinetic interactions or acute clinical safety issues preclude combination of the DPP-4 inhibitor LAF237 with glyburide. Diabetes 2004 Jun; 53 Suppl. 2: 470

    Google Scholar 

  32. Serra DB, He YL, Wang Y, et al. Combination of the DPP-4 inhibitor vildagliptin (LAF237) with pioglitazone is safe and well tolerated with no pharmacokinetic interaction. Diabetes 2005 Jun 1; 54 Suppl. 1: 528–9

    Google Scholar 

  33. He YL, Sabo R, Picard F, et al. Lack of pharmacokinetic interaction between vildagliptin and metformin in patients with type 2 diabetes. Clin Pharmacol Ther 2006 Feb; 79(2): 62

    Article  Google Scholar 

  34. Nathwani A. The use of vildagliptin for treatment of patients with type 2 diabetes mellitus. American Diabetes Association 66th Scientific Sessions; 2006 Jun 9–13; Washington, DC

  35. Mimori N, Terao S, Holmes D. Vildagliptin improves glucose control as evidenced by HbA1c after 12 weeks therapy in Japanese patients with type 2 diabetes [abstract no. 527-P]. American Diabetes Association 66th Scientific Sessions; 2006 Jun 9–13; Washington, DC

  36. DeJager S, LeBeaut A, Couturier A, et al. Sustained reduction in HbA1c during one-year treatment with vildagliptin in patients with type 2 diabetes (T2DM) [abstract no. 120-OR]. Diabetes 2006 Jun; 55 Suppl. 1: A29

    Google Scholar 

  37. DeJager S, Baron MA, Razac S, et al. Efficacy of vildagliptin in drug-naive patients with type 2 diabetes [abstract no. 0791]. Diabetologia 2006; 49 Suppl. 1: 479–80

    Google Scholar 

  38. Garber A, Camisasca RP, Ehrsam E, et al. Vildagliptin added to metformin improves glycaemic control and may mitigate metformin-induced GI side effects in patients with type 2 diabetes [abstract no. 121-OR]. Diabetes 2006 Jun; 55 Suppl. 1: A29

    Google Scholar 

  39. Baron MA, Rosenstock J, Bassiri B, et al. Efficacy of vildagliptin combined with pioglitazone in patients with type 2 diabetes [abstract no. 0801]. Diabetologia 2006; 49 Suppl. 1: 485–6

    Google Scholar 

  40. Fonseca V, DeJager S, Albrecht D, et al. Vildagliptin as add-on to insulin in patients with type 2 diabetes (T2DM) [abstract no. 467-P]. Diabetes 2006 Jun; 55 Suppl. 1: A111

    Google Scholar 

  41. Novartis. Clinical trials results database [online]. Available from URL: http://www.novartisclinicaltrials.com/ [Accessed 2006 Jul 20]

  42. Data on file. Novartis, 2006

  43. National Institute for Health and Clinical Excellence. Royal College of General Practitioners. Clinical guidelines for type 2 diabetes [online]. Available from URL: http://nice.org.uk/page.aspx?o=36881 [Accessed 2006 Oct 12]

  44. Novartis. New drug application for Galvus®, an innovative oral therapy for people with type 2 diabetes, accepted for review by FDA [online]. Available from URL: http://www.novartis.com [Accessed 2006 Jul 25]

  45. Novartis. Galvus (Rm) demonstrates powerful blood sugar reductions in Phase III studies without the side effects associated with many anti-diabetic drugs [online]. Available from URL: http://www.novartis.com [Accessed 2006 Sep 28]

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Authors and Affiliations

  1. Wolters Kluwer Health / Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 1311, New Zealand

    Sheridan Henness & Susan J. Keam

  2. Wolters Kluwer Health, Conshohocken, Pennsylvania, USA

    Sheridan Henness & Susan J. Keam

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  1. Sheridan Henness
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  2. Susan J. Keam
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Correspondence to Sheridan Henness.

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Henness, S., Keam, S.J. Vildagliptin. Drugs 66, 1989–2001 (2006). https://doi.org/10.2165/00003495-200666150-00007

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