Priorities in effective and safe glycemic control: Alogliptin in type 2 diabetes mellitus treatment
https://doi.org/10.21518/ms2025-166
Abstract
Type 2 diabetes mellitus (T2DM) is a severe disease associated with the development of serious chronic complications without targeted glycemic control. Discussion of issues of effective and affordable treatment of T2DM is of the most immediate interest. Recent years have seen a significant expansion of the glucose-lowering drug arsenal, which resulted from a deeper insight into the mechanisms of diabetes mellitus development. The significance of the entero-insular axis (EIA), the incretin system (glucagon-like peptide type 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP)) in the regulation of carbohydrate metabolism has been discovered. Inhibitors of dipeptidyl peptidase-4 (DPP-4is), also known as “gliptins”, belong to the group of incretin-based glucose-lowering drugs. The article discusses the mechanisms of action of DPP-4is and highlights the advantages of this group of drugs. Gliptins act on the major pathophysiological defect in T2DM – pancreatic β-cell dysfunction. GLP-1 is the most important for their glucose-lowering action. DPP-4is extend the half-life and availability of endogenous GLP-1 by inhibiting DPP-4. The use of DPP-4is is not accompanied by the development of hypoglycemia or weight gain, and is included in the algorithms for treating the disease in the early stages of T2DM. The article is devoted to the choice of the right drug from the DPP-4is group. It presents the results of clinical studies evaluating the efficacy, tolerability and safety of alogliptin, and data from studies comparing alogliptin with other glucose-lowering drugs. The therapeutic advantages of alogliptin are discussed. The drug has shown its effectiveness as monotherapy and as part of combination therapy in T2DM. The advantages of alogliptin and metformin combination are considered. The multi-directional action of these drugs on the pathogenetic mechanisms of T2DM leads to an increase in pharmacological effects. The importance of rational combinations of glucose-lowering drugs is emphasized. The information provided in the review concerning effective and safe glycemic control in patients with T2DM should help health professionals to make decisions in their daily clinical practice.
About the Authors
E. V. BiryukovaRussian Federation
Elena V. Biryukova, Dr. Sci. (Med.), Professor of the Department of Endocrinology and Diabetology
4, Dolgorukovskaya St., Moscow, 127006, Russia
I. V. Solovyeva
Russian Federation
Inna V. Solovyeva, Assistant of the Department of Endocrinology and Diabetology; Head of the Endocrinology Department
4, Dolgorukovskaya St., Moscow, 127006, Russia
1, Novogireevskaya St., Moscow, 111123, Russia
I. A. Averkova
Russian Federation
Irina A. Averkova, Assistant of the Department of Endocrinology and Diabetology
4, Dolgorukovskaya St., Moscow, 127006, Russia
References
1. Lovic D, Piperidou A, Zografou I, Grassos H, Pittaras A, Manolis A. The Growing Epidemic of Diabetes Mellitus. Curr Vasc Pharmacol. 2020;18(2):104–109. https://doi.org/10.2174/1570161117666190405165911.
2. Gerstein HC, Santaguida P, Raina P, Morrison KM, Balion C, Hunt D et al. Annual incidence and relative risk of diabetes in people with various categories of dysglycemia: a systematic overview and meta-analysis of prospective studies. Diabetes Res Clin Pract. 2007;78(3):305–312. https://doi.org/10.1016/j.diabres.2007.05.004.
3. DeMarsilis A, Reddy N, Boutari C, Filippaios A, Sternthal E, Katsiki N, Mantzoros C. Pharmacotherapy of type 2 diabetes: An update and future directions. Metabolism. 2022;137:155332. https://doi.org/10.1016/j.metabol.2022.155332.
4. Lu X, Xie Q, Pan X, Zhang R, Zhang X, Peng G et al. Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy. Signal Transduct Target Ther. 2024;9(1):262. https://doi.org/10.1038/s41392-024-01951-9.
5. Rizzo M, Nauck MA, Mantzoros CS. Incretin-based therapies in 2021 – Current status and perspectives for the future. Metabolism. 2021;122:154843. https://doi.org/10.1016/j.metabol.2021.154843.
6. Sesti G, Avogaro A, Belcastro S, Bonora BM, Croci M, Daniele G et al. Ten years of experience with DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. Acta Diabetol. 2019;56(6):605–617. https://doi.org/10.1007/s00592-018-1271-3.
7. Deacon CF. Dipeptidyl peptidase 4 inhibitors in the treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2020;16(11):642–653. https://doi.org/10.1038/s41574-020-0399-8.
8. Gallwitz B. Clinical Use of DPP-4 Inhibitors. Front Endocrinol. 2019;10:389. https://doi.org/10.3389/fendo.2019.00389.
9. Hernández C, Bogdanov P, Corraliza L, Garcia-Ramirez M, Sola-Adell C, Arranz JA et al. Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes. Diabetes. 2016;65(1):172–187. https://doi.org/10.2337/db15-0443.
10. Mari A, Sallas WM, He YL, Watson C, Ligueros-Saylan M, Dunning BE 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;90(8):4888–4894. https://doi.org/10.1210/jc.2004-2460.
11. Ahrén B. DPP-4 inhibitors. Best Pract Res Clin Endocrinol Metab. 2007;21(4):517–533. https://doi.org/10.1016/j.beem.2007.07.005.
12. Capuano A, Sportiello L, Maiorino MI, Rossi F, Giugliano D, Esposito K. Dipeptidyl peptidase-4 inhibitors in type 2 diabetes therapy – focus on alogliptin. Drug Des Devel Ther. 2013;7:989–1001. https://doi.org/10.2147/DDDT.S37647.
13. Johns E, McKay G, Fisher M. Dipeptidyl peptidase-4 (DPP-4) inhibitors. Br J Cardiol. 2017;24:(1). https://doi.org/10.5837/bjc.2017.001.
14. Panda SP. Role of DPP4 and DPP4i in Glucose Homeostasis and Cardiorenal Syndrome. Endocr Metab Immune Disord Drug Targets. 2023;23(2):179–187. https://doi.org/10.2174/1871530322666220531123116.
15. Cho YK, Kang YM, Lee SE, Lee J, Park JY, Lee WJ et al. Efficacy and safety of combination therapy with SGLT2 and DPP4 inhibitors in the treatment of type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab. 2018;44(5):393–401. https://doi.org/10.1016/j.diabet.2018.01.011.
16. Dedov II, Shestakova MV, Mayorov AYu, Mokrysheva NG, Andreeva EN, Bezlepkina OB et al. Standards of Specialized Diabetes Care / Edited by Dedov I.I., Shestakova M.V., Mayorov A.Yu. 11th Edition. Diabetes Mellitus. 2023;26(2S):1–157. (In Russ.) https://doi.org/10.14341/DM13042.
17. Lyu X, Zhu X, Zhao B, Du L, Chen D, Wang C et al. Effects of dipeptidyl peptidase-4 inhibitors on beta-cell function and insulin resistance in type 2 diabetes: meta-analysis of randomized controlled trials. Sci Rep. 2017;7:44865. https://doi.org/10.1038/srep44865.
18. Shestakova MV, Shestakova EA, Kachko VA. Specific features of the use of alogliptin in various groups of patients with type 2 diabetes mellitus: additional results of the ENTIRE study. Problemy Endokrinologii. 2020;66(2):49–60. (In Russ.) https://doi.org/10.14341/probl12273.
19. Godinho R, Mega C, Teixeira-de-Lemos E, Carvalho E, Teixeira F, Fernandes R, Reis F. The Place of Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Therapeutics: A “Me Too” or “the Special One” Antidiabetic Class? J Diabetes Res. 2015;2015:806979. https://doi.org/10.1155/2015/806979.
20. Shabnam M, Uddin MM, Islam MK, Hossain T, Fattah SA. Prescribing Patterns of Dipeptidyl Peptidase-4 (DPP-4) Inhibitors in Type-2 Diabetes Mellitus: A Cross-sectional Observational Study. J Green Life Med Col. 2022;7(2):61–67. Available at: https://www.researchgate.net/publication/388353453_Original_Article_on_DPP_IV_Inhibitor.
21. Saisho Y. Alogliptin benzoate for management of type 2 diabetes. Vasc Health Risk Manag. 2015;11:229–243. https://doi.org/10.2147/VHRM.S68564.
22. Scott LJ. Alogliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs. 2010;70(15):2051–2072. https://doi.org/10.2165/11205080-000000000-00000.
23. Morgunov LYu. Alogliptin: efficiency, safety, new possibilities. Meditsinskiy Sovet. 2020;(7):42–49. (In Russ.) https://doi.org/10.21518/2079-701X-2020-7-42-49.
24. DeFronzo RA, Fleck PR, Wilson CA, Mekki Q. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes and inadequate glycemic control: a randomized, double-blind, placebocontrolled study. Diabetes Care. 2008;31(12):2315–2317. https://doi.org/10.2337/dc08-1035.
25. White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369(14):1327–1335. https://doi.org/10.1056/NEJMoa1305889.
26. Fadeev VV. Results of the First Retrospective Study of Alogliptin Compared with Other Oral Hypoglycemic Drugs in Patients with Type 2 Diabetes Mellitus in Russia ARRIVAL. Effective Pharmacotherapy. 2023;19(12):6–14. (In Russ.) https://doi.org/10.33978/2307-3586-2023-19-12-6-14.
27. McCreight LJ, Bailey CJ, Pearson ER. Metformin and the gastrointestinal tract. Diabetologia. 2016;59(3):426–435. https://doi.org/10.1007/s00125-015-3844-9.
28. LaMoia TE, Shulman GI. Cellular and Molecular Mechanisms of Metformin Action. Endocr Rev. 2021;42(1):77–96. https://doi.org/10.1210/endrev/bnaa023.
29. Del Prato S, Camisasca R, Wilson C, Fleck P. Durability of the efficacy and safety of alogliptin compared with glipizide in type 2 diabetes mellitus: a 2-year study. Diabetes Obes Metab. 2014;16(12):1239–1246. https://doi.org/10.1111/dom.12377.
30. Ji L, Li L, Kuang J, Yang T, Kim DJ, Kadir AA et al. Efficacy and safety of fixeddose combination therapy, alogliptin plus metformin, in Asian patients with type 2 diabetes: A phase 3 trial. Diabetes Obes Metab. 2017;19(5):754–758. https://doi.org/10.1111/dom.12875.
31. Khunti S, Khunti K, Seidu S. Therapeutic inertia in type 2 diabetes: prevalence, causes, consequences and methods to overcome inertia. Ther Adv Endocrinol Metab. 2019;10:2042018819844694. https://doi.org/10.1177/2042018819844694.
32. Davies MJ, Drexel H, Jornayvaz FR, Pataky Z, Seferović PM, Wanner C. Cardiovascular outcomes trials: a paradigm shift in the current management of type 2 diabetes. Cardiovasc Diabetol. 2022;21(1):144. https://doi.org/10.1186/s12933-022-01575-9.
33. Koufakis T, Zografou I, Doumas M, Kotsa K. The Current Place of DPP4 Inhibitors in the Evolving Landscape of Type 2 Diabetes Management: Is It Time to Bid Adieu? Am J Cardiovasc Drugs. 2023;23(6):601–608. https://doi.org/10.1007/s40256-023-00610-8.
Review
For citations:
Biryukova EV, Solovyeva IV, Averkova IA. Priorities in effective and safe glycemic control: Alogliptin in type 2 diabetes mellitus treatment. Meditsinskiy sovet = Medical Council. 2025;(6):256-264. (In Russ.) https://doi.org/10.21518/ms2025-166