The Discovery and Development of Glucagon-Like Peptide-1 Receptor Agonists

Overview

Journal Curr Med Chem

Publisher Bentham Science Publishers

Specialty Chemistry

Date 2023 Apr 16

PMID 37062063

Authors

Haowen Fang

Bing Niu

Qin Chen

Affiliations

Soon will be listed here.

Abstract

Diabetes mellitus has become a serious life-threatening disease. As one of the new drugs for the treatment of diabetes, GLP-1 receptor agonists have attracted a lot of attention. Compared with traditional hypoglycemic drugs, GLP-1 receptor agonists have good safety and tolerability. To a certain extent, they overcome the problem of the short half-life of natural GLP-1 and can exist stably in patients for a long time, achieving good results in the treatment of diabetes, as well as improving the symptoms of some complications. The GLP-1 receptor agonists in the market are all peptide drugs. Compared with peptide drugs, small molecule agonists have the advantages of low cost and oral administration. In this article, we review the recent research progress of GLP-1 receptor agonists.

Citing Articles

Research Progress on Peptide Drugs for Type 2 Diabetes and the Possibility of Oral Administration.

Yang X, Lin R, Feng C, Kang Q, Yu P, Deng Y Pharmaceutics. 2024; 16(11).

PMID: 39598478 PMC: 11597531. DOI: 10.3390/pharmaceutics16111353.

Novel Glucagon-like Peptide 1 Receptor Agonists for Treating Type II Diabetes.

Sabnis R ACS Med Chem Lett. 2024; 15(8):1182-1183.

PMID: 39140072 PMC: 11318100. DOI: 10.1021/acsmedchemlett.4c00303.

References

Bell G, Santerre R, Mullenbach G . Hamster preproglucagon contains the sequence of glucagon and two related peptides. Nature. 1983; 302(5910):716-8. DOI: 10.1038/302716a0. View

Drucker D . Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1. Cell Metab. 2018; 27(4):740-756. DOI: 10.1016/j.cmet.2018.03.001. View

Smith N, Hackett T, Galli A, Flynn C . GLP-1: Molecular mechanisms and outcomes of a complex signaling system. Neurochem Int. 2019; 128:94-105. PMC: 7081944. DOI: 10.1016/j.neuint.2019.04.010. View

Holst J . The physiology of glucagon-like peptide 1. Physiol Rev. 2007; 87(4):1409-39. DOI: 10.1152/physrev.00034.2006. View

Ahren B . GLP-1 for type 2 diabetes. Exp Cell Res. 2011; 317(9):1239-45. DOI: 10.1016/j.yexcr.2011.01.010. View

Nauck M, Quast D, Wefers J, Meier J . GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art. Mol Metab. 2020; 46:101102. PMC: 8085572. DOI: 10.1016/j.molmet.2020.101102. View

Tornehave D, Kristensen P, Romer J, Knudsen L, Heller R . Expression of the GLP-1 receptor in mouse, rat, and human pancreas. J Histochem Cytochem. 2008; 56(9):841-51. PMC: 2516959. DOI: 10.1369/jhc.2008.951319. View

Cong Z, Chen L, Ma H, Zhou Q, Zou X, Ye C . Molecular insights into ago-allosteric modulation of the human glucagon-like peptide-1 receptor. Nat Commun. 2021; 12(1):3763. PMC: 8213797. DOI: 10.1038/s41467-021-24058-z. View

Goke R, Fehmann H, Linn T, Schmidt H, Krause M, Eng J . Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells. J Biol Chem. 1993; 268(26):19650-5. View

10.

Wang L, Liu X, Yang W, Lai J, Yu X, Liu J . Comparison of Blood Glucose Variability Between Exenatide and Biphasic Insulin Aspart 30 in Chinese Participants with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy: A Multicenter, Open-Label, Randomized Trial. Diabetes Ther. 2020; 11(10):2313-2328. PMC: 7509011. DOI: 10.1007/s13300-020-00904-z. View

11.

van der Aart-van der Beek A, van Raalte D, Guja C, Hoogenberg K, Suchower L, Hardy E . Exenatide once weekly decreases urinary albumin excretion in patients with type 2 diabetes and elevated albuminuria: Pooled analysis of randomized active controlled clinical trials. Diabetes Obes Metab. 2020; 22(9):1556-1566. PMC: 7496075. DOI: 10.1111/dom.14067. View

12.

Zhang J, Xian T, Wu M, Li C, Pan Q, Guo L . Comparison of the effects of twice-daily exenatide and insulin on carotid intima-media thickness in type 2 diabetes mellitus patients: a 52-week randomized, open-label, controlled trial. Cardiovasc Diabetol. 2020; 19(1):48. PMC: 7183674. DOI: 10.1186/s12933-020-01014-7. View

13.

Retnakaran R, Ye C, Emery A, Kramer C, Zinman B . The metabolic effects of adding exenatide to basal insulin therapy when targeting remission in early type 2 diabetes in a randomized clinical trial. Nat Commun. 2022; 13(1):6109. PMC: 9573864. DOI: 10.1038/s41467-022-33867-9. View

14.

Tamborlane W, Bishai R, Geller D, Shehadeh N, Al-Abdulrazzaq D, Vazquez E . Once-Weekly Exenatide in Youth With Type 2 Diabetes. Diabetes Care. 2022; 45(8):1833-1840. PMC: 9346995. DOI: 10.2337/dc21-2275. View

15.

Jones K, Rigda R, Buttfield M, Hatzinikolas S, Pham H, Marathe C . Effects of lixisenatide on postprandial blood pressure, gastric emptying and glycaemia in healthy people and people with type 2 diabetes. Diabetes Obes Metab. 2019; 21(5):1158-1167. DOI: 10.1111/dom.13633. View

16.

Rayner C, Watson L, Phillips L, Lange K, Bound M, Grivell J . Effects of Sustained Treatment With Lixisenatide on Gastric Emptying and Postprandial Glucose Metabolism in Type 2 Diabetes: A Randomized Controlled Trial. Diabetes Care. 2020; 43(8):1813-1821. DOI: 10.2337/dc20-0190. View

17.

Gerstein H, Hess S, Claggett B, Dickstein K, Kober L, Maggioni A . Protein Biomarkers and Cardiovascular Outcomes in People With Type 2 Diabetes and Acute Coronary Syndrome: The ELIXA Biomarker Study. Diabetes Care. 2022; 45(9):2152-2155. DOI: 10.2337/dc22-0453. View

18.

Yang W, Dong X, Li Q, Cheng Z, Yuan G, Liu M . Efficacy and safety benefits of iGlarLixi versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with suboptimally controlled type 2 diabetes on oral agents: The LixiLan-O-AP randomized controlled trial. Diabetes Obes Metab. 2022; 24(8):1522-1533. DOI: 10.1111/dom.14722. View

19.

Ferrannini E, Niemoeller E, Dex T, Servera S, Mari A . Fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) improves ß-cell function in people with type 2 diabetes. Diabetes Obes Metab. 2022; 24(6):1159-1165. PMC: 9314929. DOI: 10.1111/dom.14688. View

20.

Davies M, Rosenstock J, Ali A, Russell-Jones D, Souhami E, Palmer K . Efficacy of iGlarLixi in adults with type 2 diabetes inadequately controlled (glycated haemoglobin ≥8%, ≥64 mmol/mol) on two oral antidiabetes drugs: Post hoc analysis of the LixiLan-O randomized trial. Diabetes Obes Metab. 2021; 24(1):34-41. PMC: 9293415. DOI: 10.1111/dom.14543. View