10 years of experience with vildagliptin in Russian medical practice: clinical examples of new possibilities

• Alexander S. Ametov
• Anna O. Nevolnikova
• Ekaterina A. Tertychnaya

Abstract

Type 2 diabetes mellitus (T2DM) is a severe chronic disease that poses a serious medical and social problem worldwide. The modern concept of effective and safe management of T2DM is pathogenetic. To date, 11 pathophysiological mechanisms of hyperglycemia in T2DM have been identified, which are united by a "common denominator" - a genetically damaged β-cell with a subsequent decrease in secretory activity. Therapeutic approaches to T2DM consist in the use of drugs that, when monotherapy or in complementary combinations, correct the maximum number of pathophysiological disorders. A multifactorial comprehensive approach allows achieving stable stabilization of glycemia, preserving the functional reserve of β-cells and reducing cardiovascular risk in patients. A new window of pharmacotherapeutic opportunities has become a group of drugs that affect intestinal hormones - incretins.

In healthy individuals the secretion of incretins provides 50-70% of postprandial insulin. In patients with T2DM, a decrease in the incretin effect is observed. This became the basis for the development of a new class of hypoglycemic drugs - type 4 dipeptidylpetidase inhibitors (DPP-4), which convincingly showed the effect on 7 pathogenetic mechanisms of T2DM. In 2008, vildagliptin, the first representative of DPP-4 inhibitors, was registered in the Russian Federation. The physiological glucose-dependent action along with pleiotropic properties determine the high efficiency and complementarity of vildagliptin when used both in monotherapy and in various oral anidiabetes drugs combinations. Combination therapy with vildagliptin and metformin affects 10 of the 11 pathogenetic mechanisms of development of T2DM, providing a longer target glycemic control. The authors presented six clinical cases of successful use of vildagliptin in the practice of an outpatient endocrinologist. They reveal in detail the various facets of the possibilities of this drug in the management of T2DM and improve the quality of life of our patients.

Keywords:type 2 diabetes mellitus, β-cell dysfunction, pathogenetic mechanisms of diabetes mellitus 2, incretins, vildagliptin

References

1. Nobel Lectures, Physiology or Medicine 1922-1941. Amsterdam: Elsevier Publishing Company; 1965.

2. IDF Diabetes Atlas, 2017.

3. Dedov I.I., Shestakova M.V., Galstyan G.R. The prevalence of type 2 diabetes mellitus in the adult population of Russia (NATION study). Sakharniy diabet [Diabetes Mellitus]. 2016; 19 (2): 104-12. (in Russian)

4. Ametov A.S. Type 2 Diabetes Mellitus. Problems and Solutions. Moscow: GEOTAR-Media, 2015; 1: 352 p. (in Russian)

5. United Kingdom 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.

6. Skyler S., Bergenstal R., Bonow R., et al. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA Diabetes Trials. Diabetes Care. 2009; 32 (1): 187-92.

7. Shwartz S.S., Epstein S., Corkey B., et al. The time is right for a new classification system for diabetes: rationale and implications of the b-cell-centric classification schema. Diabetes Care. 2016; 39: 179-86. doi: 10.2337/dc15-1585

8. Standards of specialized diabetes care. In: I.I. Dedov, M.V. Shestakova, A.Yu. Mayorov. 9th ed. Sakharniy diabet [Diabetes Mellitus]. 2019; 22 (S1). doi: 10.14341/DM221S1 (in Russian)

9. Holst J.J., Windelov J.A., Boer G.A., et al. Searching for the physiological role of glucose-dependent insulinotropic polypeptide. J Diabetes Investig. 2016; 7: 8-12. doi: 10.1111/jdi.12488

10. Rehfeld J.F. The origin and understanding of the incretin concept. Front Endocrinol (Lausanne). 2018; 9: 387. doi: 10.3389/ fendo.2018.00387

11. Nauck M.A., Meier J.J. The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions. Lancet Diabetes Endocrinol. 2016; 4 (6): 52536. doi: 10.1016/S2213-8587(15)00482-9

12. Deacon C.F., Johnsen A.H., Holst 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 (3): 952-7.

13. Rothenberg P., Kalbag J.,Smith H., Gigerich R., et al. Treatment with a DPP-IV inhibitor, NVP-Dpp 728, increases prandial intact GLP-1 levels and reduces glucose exposure in humans. Diabetes. 2000; 49 (suppl 1): 39.

14. Ahren B., Simonsson E., Larsson H., Landin-Olsson M., et al. Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes. Diabetes Care. 2002; 25: 869-75.

15. Wilhauer E. Vildagliptin: the first innovative DDP-4 inhibitor. Sakharniy diabet [Diabetes Mellitus]. 2010; 13 (3): 118-20. URL: https://doi.org/10.14341/2072-0351-5499 (in Russian)

16. Ametov A.S. Vildagliptin: optimal control in type 2 diabetes mel-litus treatment. Sakharniy diabet [Diabetes Mellitus]. 201; 18 (4): 125-9. (in Russian)

17. Ametov A.S. Type 2 Diabetes Mellitus. Problems and Solutions. Moscow: GEOTAR-Media, 2015; 4: 312 p. (in Russian)

18. Williams R., de Vries F., Kothny W., et al. Cardiovascular safety of vildagliptin in patients with type 2 diabetes: a European multi-database, non-interventional post-authorization safety study. Diabetes Obes Metab. 2017; 19 (10): 1473-8. doi: 10.1111/dom.12951

19. Tani S., Nagao K., Hirayama A. Association between urinary albumin excretion and low-density lipoprotein heterogeneity following treatment of type 2 diabetes patients with the dipeptidyl peptidase-4 inhibitor, vildagliptin: a pilot study. Am J Cardiovasc Drugs. 2013; 13 (6): 443-50.

20. Ishii M., Shibata R., Kondo K. Vildagliptin stimulates endothelial cell network formation and ischemia-induced revascularization via an endothelial nitric-oxide synthase-dependent mechanism. J Biol Chem. 2014; 289 (39): 27 235-45.

21. Matthews D.R., Pald P.M., Proot P., Foley J.E., et al. Glycaemic durability of an early combination therapy with vildagliptin and metformin versus sequential metformin monotherapy in newly diagnosed type 2 diabetes (VERIFY): a 5-year, multicentre, randomised, double-blind trial. Lancet. 2019 Sept 17. URL: https://doi.org/10.1016/S0140-6736(19)32131-2

22. Goke B., Hershon K., Kerr D., et al. Efficacy and safety of vildagliptin monotherapy during 2-year treatment of drug-naive patients with type 2 diabetes: comparison with metformin. Horm Metab Res. 2008; 40 (12): 892-5. doi: https://doi.org/10.1055/s-0028-1082334

23. Mclnnes G., Evans M., Del Prato S., Stumvoll M., et al. Cardiovascular and heart failure safety profile of vildagliptin: a meta-analysis of 17 000 patients. Diabetes Obes Metab. 2015; 17 (11): 1085-92. doi: 10.1111/dom.12548

24. Kanazawa I., Tanaka K.I., Notsu M., et al. Long-term efficacy and safety of vildagliptin add-on therapy in type 2 diabetes mellitus with insulin treatment. Diabetes Res Clin Pract. 2017; 123: 9-17.

25. Rosenstock J., Hansen L., Zee P., Li Y., et al. Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: a randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin. Diabetes Care. 2015; 38 (3): 376-83. doi: 10.2337/dc14-1142

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)