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3 . 2022

Niche of the dipeptidyl peptidase 4 inhibitor alogliptin in hypoglycemic therapy of type 2 diabetes mellitus

Abstract

The article provides an overview of the main drugs prescribed during management of patients with type 2 diabetes mellitus (T2DM) and separately considers the dipeptidyl peptidase‑4 (DPP‑4) inhibitor alogliptin.

For many years, it has been assumed that intensive glycemic control in patients with T2DM results in improved macrovascular outcomes. However, current data, on the basis of which the latest clinical guidelines for management of patients with diabetes mellitus have been formed, have led to a transition from a purely glucocentric point of view to the current safe approach focused on cardiovascular outcome and maintenance of kidney function.

DPP‑4 inhibitors, or gliptins, belong to the class of incretin mimetics. DPP‑4 inhibition leads to an increase of endogenous glucagon-like peptide‑1 (glucose-dependent insulinotropic polypeptide) activity which ultimately leads to an increase insulin secretion in pancreatic β-cells and a subsequent decrease in blood glucose levels, as well as glycated hemoglobin levels. These drugs have been widely available for the treatment of patients with T2DM for more than a decade. Glycemic control provided by DPP‑4 inhibitors leads to a decrease in glycated hemoglobin levels in case of monotherapy from 0.5 to 1.0%. In case of combination therapy with other hypoglycemic drugs, a more significant effect on the level of HbA1c can be achieved.

Keywords:diabetes mellitus; cardiovascular outcomes; hypoglycemic therapy; dipeptidyl peptidase 4 inhibitors; gliptins

Funding. The study had no sponsor support.

Conflict of interest. The authors declare no conflict of interest.

For citation: Pesheva E.D., Fadeev V.V. Niche of the dipeptidyl peptidase‑4 inhibitor alogliptin in hypoglycemic therapy of type 2 diabetes mellitus. Endokrinologiya: novosti, mneniya, obuchenie [Endocrinology: News, Opinions, Training]. 2022; 11 (3): 69–74. DOI: https://doi.org/10.33029/2304-9529-2022-11-3-69-74 (in Russian)

References

1. Holman R.R., Paul S.K., Bethel M.A., Matthews D.R., Neil H.A. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008; 359 (15): 1577–89. DOI: https://doi.org/10.1056/NEJMoa0806470

2. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352 (9131): 837–53.

3. Defronzo R.A., Mehta R.J., Schnure J.J. Pleiotropic effects of thiazolidinediones: implications for the treatment of patients with type 2 diabetes mellitus. Hosp Pract (1995). 2013; 41 (2): 132–47. DOI: https://doi.org/10.3810/hp.2013.04.1062

4. Dormandy J.A., Charbonnel B., Eckland D.J., Erdmann E., et al.; PROactive Investigators. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005; 366 (9493): 1279–89. DOI: https://doi.org/10.1016/S0140-6736(05)67528-9

5. Sinha B., Ghosal S. Assessing the need for pioglitazone in the treatment of patients with type 2 diabetes: a meta-analysis of its risks and benefits from prospective trials. Sci Rep. 2020; 10 (1): 15781. DOI: https://doi.org/10.1038/s41598-020-72967-8

6. Yaghi S., Furie K.L., Viscoli C.M., Kamel H., et al.; IRIS Trial Investigators. Pioglitazone prevents stroke in patients with a recent transient ischemic attack or ischemic stroke: a planned secondary analysis of the IRIS trial (Insulin Resistance Intervention after Stroke). Circulation. 2018; 137 (5): 455–63. DOI: https://doi.org/10.1161/CIRCULATIONAHA.117.030458

7. Nauck M.A., Ellis G.C., Fleck P.R., Wilson C.A., Mekki Q.; Alogliptin Study 008 Group. Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomised, double-blind, placebo-controlled study. Int J Clin Pract. 2009; 63 (1): 46–55. DOI: https://doi.org/10.1111/j.1742-1241.2008.01933.x

8. Pratley R.E., Fleck P., Wilson C. Efficacy and safety of initial combination therapy with alogliptin plus metformin versus either as monotherapy in drug-naïve patients with type 2 diabetes: a randomized, double-blind, 6-month study. Diabetes Obes Metab. 2014; 16 (7): 613–21. DOI: https://doi.org/10.1111/dom.12258

9. 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): 1239–46. DOI: https://doi.org/10.1111/dom.12377

10. Pratley R.E. Alogliptin: a new, highly selective dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. Expert Opin Pharmacother. 2009; 10 (3): 503–12. DOI: https://doi.org/10.1517/14656560802694713

11. Shih C.J., Chen H.T., Kuo S.C., Ou S.M., Chen Y.T. Cardiovascular outcomes of dipeptidyl peptidase-4 inhibitors in elderly patients with type 2 diabetes: a nationwide study. J Am Med Dir Assoc. 2016; 17 (1): 59–64. DOI: https://doi.org/10.1016/j.jamda.2015.10.009

12. White W.B., et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. Aust J Clin Endocrinol Metab. 2014; 2 (7): 77.

13. Spinar J., Smahelová A. SAVOR-TIMI 53 – Vysledky saxagliptinu a kardiovaskularni vysledky u pacientu s diabetes mellitus 2 typu [SAVOR TIMI 53 –  Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus]. Vnitr Lek. 2013; 59 (11): 1003–7. (in Czech)

14. Cornel J.H. Bakris G.L., Stevens S.R., Alvarsson M., Bax W.A., Chuang L.M., et al. Effect of sitagliptin on kidney function and respective cardiovascular outcomes in type 2 diabetes: outcomes from TECOS. Diabetes Care. 2016; 39 (12): 2304–10.

15. Perkovic V., Toto R., Cooper M.E., Mann J.F.E., Rosenstock J., McGuire D.K., CARMELINA investigators. Effects of linagliptin on cardiovascular and kidney outcomes in people with normal and reduced kidney function: secondary analysis of the carmelina randomized trial. Diabetes Care. 2020; 43 (8): 1803–12.

16. Terasaki M., Nagashima M., Nohtomi K., et al. Preventive effect of dipeptidyl peptidase-4 inhibitor on atherosclerosis is mainly attributable to incretin’s actions in nondiabetic and diabetic apolipoprotein E-null mice. PLoS One. 2013; 8 (8): 1–12.

17. Zeng Y., Li C., Guan M., Zheng Z., Li J., Xu W., et al. The DPP-4 inhibitor sitagliptin attenuates the progress of atherosclerosis in apolipoprotein-E-knockout mice via AMPK- and MAPK-dependent mechanisms. Cardiovasc Diabetol. 2014; 13 (1): 1–10.

18. Mita T., Katakami N., Yoshii H., et al. Alogliptin, a dipeptidyl peptidase 4 inhibitor, prevents the progression of carotid atherosclerosis in patients with type 2 diabetes: the Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A). Diabetes Care. 2016; 39 (1): 139–48.

19. Langenfeld M.R., Forst T., Hohberg C., et al. Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with type 2 diabetes mellitus: results from a controlled randomized study. Circulation. 2005; 111 (19): 2525–31.

20. Walker S.R., Komenda P., Khojah S., et al. Dipeptidyl peptidase-4 inhibitors in chronic kidney disease: a systematic review of randomized clinical trials. Nephron. 2017; 136 (2): 85–94.

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CHIEF EDITOR
CHIEF EDITOR
Ametov Alexander S.
Honored Scientist of the Russian Federation, Doctor of Medical Sciences, Professor, Head of Subdepartment of Endocrinology, Head of the UNESCO Network Chair on the subject «Bioethics of diabetes as a global problem» of the Russian Medical Academy of Continuous Professional Education (Moscow)
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