Decrease in the efficacy of glucagon-like peptide-1 receptor agonists: what is the reason?

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Published: Jan 14, 2022
DOI: https://doi.org/10.22141/2224-0721.17.8.2021.246799
Keywords:
glucagon-like peptide receptor agonists, tachyphylaxis, modified analogs, antibodies to glucagon-like peptide-1 receptor agonists, intestinal microbiota, review

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N.M. Kushnarova
State Institution “V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Science of Ukraine”, Kyiv, Ukraine
https://orcid.org/0000-0002-5390-6784
O.V. Zinych
State Institution “V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Science of Ukraine”, Kyiv, Ukraine
https://orcid.org/0000-0002-0516-0148
V.V. Korpavchev
State Institution “V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Science of Ukraine”, Kyiv, Ukraine
https://orcid.org/0000-0003-0182-9753
A.V. Kovalchuk
State Institution “V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Science of Ukraine”, Kyiv, Ukraine
https://orcid.org/0000-0001-6591-1460
O.V. Prybyla
State Institution “V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Science of Ukraine”, Kyiv, Ukraine
https://orcid.org/0000-0003-2212-1172
K.O. Shyshkan-Shishova
State Institution “V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Science of Ukraine”, Kyiv, Ukraine
https://orcid.org/0000-0003-0939-5902

Abstract

The review deals with the drugs of a group of glucagon-like peptide-1 receptors agonists (GLP-1RA) the action of which is based on the incretin effect. In addition to insulinotropic and glucagonostatic action, GLP-1RA contributes to the improvement of glycemic control, a decrease in body weight, and also reduces cardiovascular effects in diabetic patients. The members of this group are divided into short- and long-acting preparations that is determined by their pharmacodynamic properties. Studies have shown that the long-acting GLP-1RA, which are administered once a week, demonstrate better glycemic control with a similar or less risk of the hypoglycemia and gastrointestinal side effects than their short-acting analogues. However, with long-term use of GLP-1RA, there is a reduction in the hypoglycemic action associated with a decrease in the inhibition of intestinal motility due to the phenomenon of tachyphylaxis (desensitization) of the GLP-1 receptors as a result of the vagus nerve activation. Promising means to overcome this shortcoming are considered, such as the development of modified and combined coagonists of dipeptidyl peptidase 1 receptors, as well as oral forms of GLP-1RA. In addition, we have described possible mechanisms influencing the effectiveness of GLP-1RA due to the production of antibodies to various drugs in this group, and the relationship between the effects of incretin mimetics with the state of the intestinal microbiota. In conclusion, the group of incretin-based drugs provides broad perspectives for use in type 2 diabetic patients, with the possibility of correction of both basal and prandial glycemia, and new efficient and safe forms of drugs of this group are actively creating.

Article Details

How to Cite
Kushnarova, N., O. Zinych, V. Korpavchev, A. Kovalchuk, O. Prybyla, and K. Shyshkan-Shishova. “Decrease in the Efficacy of Glucagon-Like Peptide-1 Receptor Agonists: What Is the Reason?”. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), vol. 17, no. 8, Jan. 2022, pp. 637-45, doi:10.22141/2224-0721.17.8.2021.246799.
Issue
Vol. 17 No. 8 (2021)
Section
Literature Review
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