Pathogenetic substantiation and effectiveness of vildagliptin use inpatients with diabetes mellitus type 2
https://doi.org/10.14341/2071-8713-5241
Abstract
Insulin resistance in muscle and liver and β-cell failure represent the core pathophysiologic defects in type 2 diabetes. Now it isrecognized that the β-cell failure occurs much earlier and is more severe than previously thought. As a result, earlier and more aggressive new therapy is needed to achiev e better control of diabetes and to prev ent/slow the progressive B-cell failure that already is w ell established in IGT subjects. One approach is to target the incretin mimetic hormone glucagon-like peptide-1 (GLP-1). When blood glucose levels are elevated, GrP-1 stimulates insulin secretion, decreases glucagon secretion, impro ves β-cell function, and slows gastric emptying. GrP-1 production is reduced in patients with type 2 diabetes. Furthermore, GrP-1 is rapidly degraded by the dipeptidyl peptidase 4 (DPP-4) enzyme. Trials have showed, that new inhibitor DPP-4 vildagliptin (Galvus) hav e been demonstrated to significantly reduce HbA lc, fasting and prandial glucose levels when used as monotherapy and in соmbination with traditional agents. Advantages of vildagliptin include few adverse events, low risk of hypoglycemia, neutral effect on body weight, and a once-daily oral dosing regimen. Inaddition, vildagliptin may preserve the decline in β-cell function. Hence, vildagliptin may modify the natural progressive course of diabetes; this however, must be confirmed with longer-term controlled studies
References
1. Abdul-Ghani M., Tripathy D., DeFronzo R.A. Contributions of -cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes Care 2006; 29:1130- 39.
2. Ahren В., Gomis R., Standi E. et al. Twelve- and 52-weeks efficacy of the dipeptidyl peptidase IV inhibitor LAF23 7 in metform in-treated patients wi th type 2 diabetes. Diabetes Care 2004; 27:2874-80.
3. Ahren B. Vildagliptin: an inhibitor of dipeptidyl peptidase-4 with antidiabetic properties. Exp. Opin. Invest. Drugs. 2006; 15:431-442.
4. Ahren B.DPP-4 inhibitors Best Pract. Res. Clin. Endocrinol. Metab. 2007; 21(4): 517-33.
5. Amori R.E., Lau J., Pittas AG.Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA 2007; 298:194-206.
6. Baggio L.L., Huang Q., Brown T.J., Drucker D.J. Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure. Gastroenterology 2004;127:546-58.
7. Baggio L.L., Drucker D.J. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007;132:2131-57.
8. Bose A.K., Mocanu M.M., Carr R.D. et al.Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. Diabetes 2005; 54:146-51.
9. Bosi E., Camisaca R.P., Collober С. et al.Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin. Diabetes Care 2007; 30: 890-95.
10. Brown J.C., Dryburgh J.R., Ross S.A, Dupre J. Identification and actions of gastric inhibitory polypeptide. Recent. Prog. Horm. Res. 1975;31:487-532.
11. Burkey B.F., Russell M., Wang K. et al. Vildagliptin displays slow tight-binding to dipeptidyl peptidase (DPP)-4, but not DPP-8 or DPP-9.42nd European Association of the Study of Diabetes Annual Meeting. Copenhagen, Denmark - Malmoe, Sweden; 2006 Sep 14-17. Abstract.
12. Butler A.E., Janson J., Bonner-Weir S. et al.-Cell deficit and increased -cell apoptosis in humans with type 2 diabetes. Diabetes 2003; 52:102- 10.
13. Croxtall J.D., Keam S.J. Vildagliptin: a review of use in the management of type 2 diabetes mellitus. Drugs 2008; 68(16): 2387-409.
14. Cummings D.E., Overduin J. Gastrointestinal regulation of food intake. JCI 2007, 117(1): 13-23.
15. Deacon C.F., Johnsen A.H., Hoist J.J. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J. Clin. Endocrinol. Metab. 1995; 80: 952-7.
16. DeFronzo R.A. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009; 58 (4): 773-95.
17. Dejager S., Lebeaut A., Couturier A., Schweizer A. Sustained reduction in A1С during one-year treatment with vildagliptin in patients with type 2 diabetes (T2DM). Diabetes 2006; 55 (Suppl.1):A29.
18. Dejager S., Razac S., Foley J.E. et al. Vildagliptin in drug-na-ve patients with type 2 diabetes: a 24-week, double-blind, randomized, placebo-controlled, multiple-dose study. Horm. Metab. Res. 2007 21:113-8.
19. Diabetes Prevention Program Research Group. The prevalence of retinopathy in impaired glucose tolerance and recent-onset diabetes in the Diabetes Prevention Program. Diabet. Med. 2007; 24:137- 44.
20. Donath M.Y., Ehses J.A., Maedler K. et al. Mechanisms of §-cell death in type 2 diabetes. Diabetes 2005; 54(Suppl 2): 108-13.
21. Drucker D.J. Glucagon-like peptide 2 . J. Clin. Endocrinol. Metab. 2001 86(4): 1759-1764.
22. Drucker D.J.GIucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol. Endocrinol. 2003; 17(2): 161-71.
23. Duttaroy A., Voelker F., Merriam K. et al. The DPP-4 inhibitor vildagliptin increases pancreatic beta cell neogenesis and decreases apoptosis [abstract] .ADA, 65th Annual Scientific Session, 2005; San-Diego, Calif. Abstract 572-P.
24. DuttaroyA., Voelker F., Ren X. et al. Head-to-head comparison of the DPP-4 inhibitor vildagliptinwith exendin-4 in a model of pancreatic beta cell injury, [abstract]. ADA, 65th Annual Scientific Session, 2005; San-Diego, Calif. Abstract 267-OR.
25. Egan J.M., Margolskee R.F. Taste cells of the gut and gastrointestinal chemosensation Mol. Interv. 2008;8(2): 78-81.
26. Ferrannini E., Gastaldelli A., Miyazaki Y. et al. Beta cell function in subjects spanning the range from normal glucose tolerance to overt diabetes mellitus: a new analysis. J. Clin. Endocrinol. Metab. 2005; 90:493- 500.
27. Fonseca V, Dejager S., Albrecht S . et al. Vildagliptin as add-on to insulin in patients with type 2 diabetes (T2DM). Diabetes 2006; 55(suppl 1 ):A111.
28. Garber A.G., Schweizer A., Baron M.A. et al. Vildagliptin in combination withpiogli-tazone improves glycaemic control in patients with type 2 diabetes failing thiazo-lidinedione monotherapy: randomized, placebo-controlled study. Diabetes. Obes. Metab. 2007;9:166-74.
29. Halimi S., Schweizer A., Minic B. et al. Combination treatment in the management of type 2 diabetes: focus on vildagliptin and metformin as a single tablet. Vascular Health and Risk Management 2008; 4(3): 481-92.
30. Hargrove D.M., Nardone N.A., Persson L.M. et al. Glucose-dependent action of glucagon-like peptide-1(7-37) in vivo during short- or long-term administration. Metabolism 1995; 44:1231-7.
31. Henriksen D.B., Alexandersen P., Ejarnason N.H. et al. Christiansen С Role of gastrointestinal hormones in postprandial reduction of bone resorption. J. Bone. Miner. Res. 2003; 18: 2180-9.
32. Herman G.A., Bergman A, Stevens С 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 in patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 2006;91:4612-9.
33. Hoist J.J. The physiology of glucagon-like peptide-1. Physiol. Rev. 2007; 87: 1409-39.
34. Hoist J.J., Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am. J. Physiol. Endocrinol. Metab. 2004; 287: 199-206.
35. Hui H., Wright C., Perfetti R. Glucagon-like peptide 1 induces differentiation of islet duodenal homeobox-1-positive pancreatic ductal cells into insulin-secreting cells. Diabetes 2001; 50: 785 -96.
36. Idris I., Donnelly R. Dipeptidyl peptidase-IV inhibitors: a major new class of oral antidiabetic drug. Diabetes. Obes. Metab. 2007; 9:153-65.
37. Jang H.J., Kokrashvili Z., Theodorakis M.J. et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc. Natl. Acad. Sci. U.S.A. 2007;104:15069-74.
38. Larsen P. Mechanism behind GLP-1 induced weight loss. Br J Vasc Dis 2008; 8(Suppl.2): 34-41.
39. Lauritsen K.B., Moody A.J., Christensen K.C. et al. Gastric inhibitory polypeptide (GIP) and insulin release after small-bowel resection in man. Scand. J. Gastroenterol. 1980; 15: 833-40.
40. Marfella R., Barbieri M., Grella R. et al. Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-hour acute glucose fluctuations. J. Dia. Соmр. 2009,1:1-5.
41. Margolskee R.F., Dyer J., KokrashviliZ. et al. T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proc. Natl. Acad. Sci. U.S.A. 2007; 104: 15075-80.
42. Mari A., Sallas W.M., Не Y.L etal. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model assessed beta-cell function in patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 2005; 90,4888-94.
43. Mayo K.E., Miller L.J., Bataille D. et al. International Union of PharmacologyXXXV. The Glucagon Receptor Family. Pharmacol. Rev. 2003; 55:167-94.
44. Mclntyre N., Holsworth D.C., Turner D.S. New interpretation of oral glucose tolerance. Lancet 1964; 2:20-1.
45. Miyawaki K., Yamada Y., Ban N. et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat. Med. 2002;8: 738-42.
46. Moore В., Edie E.S., Abram J.H. On the treatment of diabetes mellitus by acid extract of duodenal mucous membrane. Biochem. J. 1906;1:28-38.
47. Murphy K.G., Dhillo W.S., Bloom S.R.Gut peptides in the regulation of food intake and energy homeostasis Endocr Rew 2008; 27(7): 719-27.
48. Nikolaidis L.A., Mankad S., Sokos G.G. et al. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation 2004; 109: 962-5.
49. Nyberg J., Anderson M.F., Meister B. et al. Glucose-dependent insulinotropic polypeptide is expressed in adult hippocampus and induces progenitor cell proliferation. J. Neurosci.2005; 25:1816-25.
50. Nystrom Т., Gutniak M.K., Zhang Q., et al. Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am. J. Physiol. Endocrino.l Metab. 2004; 287:1209-15.
51. Orskov C., Hoist J.J., Nielsen O.V. Effect of truncated glucagon-like peptide-1 [proglucagon- (78-107) amide] on endocrine secretion from pig pancreas, antrum, and nonantral stomach. Endocrinol. 1988; 123: 2009-13.
52. Pi-Sunyer F.X., Schweizer A., Mills D., Dejager S. Efficacy and tolerability of vildagliptin monotherapy in drug-na -ve patients with type 2 diabetes. Diabetes. Res. Clin. Pract. 2007; 76:132-8.
53. Ristic S., Byiers S., Foley J., Holmes D. Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response. Diabet. Obes. Metab. 2006; 7: 692-8.
54. Rosenstock J., Brazg R.G., Andryuk P.J. etal. 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, placebocontrolled, parallel-group study. Clinical. Ther. 2006; 28:1556-68.
55. Rosenstock J., Baron M.A., Dejager S. et al. Comparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes: a 24-week, doubleblind, randomized trial. Diabetes Care 2007; 30:217-23.
56. Rosenstock J., Zinman B. Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus. Cur. Opin. Endocrinol. Diabetes. Obes. 2007;14(2):98-107.
57. Rouille Y., Martin S., Steiner D.F. Differential processing of proglucagon by the subtilisin-like prohormone convertases PC2 and PC3 to generate either glucagon or glucagon-like peptide. J. Biol. Chem. 1995; 270: 26488-96.
58. Salehi M., Aulinger B.A., D'Alessio D.A. Targeting -cell mass in type 2 diabetes: promise and limitations of new drugs based on incretins. Endocr. Rev. 2008, 29(3): 367-79.
59. Smith A.G., Russell J., Feldman E.L. et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care 2006; 6: 415- 6.
60. Toft-Nielsen M.B., Damholt M.B., Madsbad S. et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol. Metab. 2001 ;86: 3717-23.
61. UK Prospective Diabetes Study (UKPDS) Group. 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: 837-53.
62. Vella A., Bock G., Giesler P. D. et al. The effect of to dipeptidyl peptidase-4 inhibition on gastric volume, satiation and enteroendocrine secretion in type 2 diabetes: a double-blind, placebo-controlled, crossoverstudy. Clin. Endocrinol. 2008;69(5):737-44.
63. Wajchenberg B.L. Beta-cell failure in diabetes and preservation by clinical treatment. Endocr. Rev. 2007; 28 (2): 187-218.
64. Willms В., Werner J., Hoist J.J. et al. Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7-36) amide in type 2 (noninsulin-dependent) diabetic patients. J. Clin. Endocrinol. Metab. 1996; 81:327-32.
65. Woods S.C. Dietary synergies in appetite control: distal gastrointestinal tract. Obesity 2006;14(Suppl): 171-8.
66. Zhong Q., Itokawa Т., Sridhar S. et al. Effects of glucose-dependent insulinotropic peptide on osteoclast function. Am. J. Physiol. 2007; 292: 543-8.
Review
For citations:
Pathogenetic substantiation and effectiveness of vildagliptin use inpatients with diabetes mellitus type 2. Obesity and metabolism. 2009;6(3):16-26. (In Russ.) https://doi.org/10.14341/2071-8713-5241
Views:
416
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
