» Articles » PMID: 34137731

How Glucagon-like Peptide 1 Receptor Agonists Work

Overview
Journal Endocr Connect
Specialty Endocrinology
Date 2021 Jun 17
PMID 34137731
Citations 13
Authors
Affiliations
Soon will be listed here.
Abstract

In recent years, glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become central in the treatment of type 2 diabetes (T2D). In addition to their glucose-lowering properties with low risk of hypoglycaemia, GLP-1RAs reduce body weight and show promising results in reducing cardiovascular risk and renal complications in high-risk individuals with T2D. These findings have changed guidelines on T2D management over the last years, and GLP-1RAs are now widely used in overweight patients with T2D as well as in patients with T2D and cardiovascular disease regardless of glycaemic control. The currently available GLP-1RAs have different pharmacokinetic profiles and differ in their ability to improve glycaemia, reduce body weight and in their cardio- and renal protective potentials. Understanding how these agents work, including insights into their pleiotropic effects on T2D pathophysiology, may improve their clinical utilisation and be useful for exploring other indications such as non-alcoholic steatohepatitis and neurodegenerative disorders. In this review, we provide an overview of approved GLP-1RAs, their clinical effects and mode of action, and we offer insights into the potential of GLP-1RAs for other indications than T2D. Finally, we will discuss the emerging data and therapeutic potential of using GLP-1RAs in combinations with other receptor agonists.

Citing Articles

Hallmarks of Appetite: A Comprehensive Review of Hunger, Appetite, Satiation, and Satiety.

Garutti M, Sirico M, Noto C, Foffano L, Hopkins M, Puglisi F Curr Obes Rep. 2025; 14(1):12.

PMID: 39849268 DOI: 10.1007/s13679-024-00604-w.


GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes: Pleiotropic Cardiometabolic Effects and Add-on Value of a Combined Therapy.

Scheen A Drugs. 2024; 84(11):1347-1364.

PMID: 39342059 DOI: 10.1007/s40265-024-02090-9.


Glucagon-like peptide-1 receptor: mechanisms and advances in therapy.

Zheng Z, Zong Y, Ma Y, Tian Y, Pang Y, Zhang C Signal Transduct Target Ther. 2024; 9(1):234.

PMID: 39289339 PMC: 11408715. DOI: 10.1038/s41392-024-01931-z.


Beyond Glycemic Control: GLP-1 Receptor Agonists and Their Impact on Calcium Homeostasis in Real-World Patients.

Alenezi B, Elfezzani N, Uddin R, Patel H, Chester S, Abdelmaksoud A J Clin Med. 2024; 13(16).

PMID: 39201039 PMC: 11355112. DOI: 10.3390/jcm13164896.


Implications of GLP-1 Receptor Agonist on Thyroid Function: A Literature Review of Its Effects on Thyroid Volume, Risk of Cancer, Functionality and TSH Levels.

Capuccio S, Scilletta S, La Rocca F, Miano N, Di Marco M, Bosco G Biomolecules. 2024; 14(6).

PMID: 38927090 PMC: 11202033. DOI: 10.3390/biom14060687.


References
1.
Thomas M, Nikooienejad A, Bray R, Cui X, Wilson J, Duffin K . Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. J Clin Endocrinol Metab. 2020; 106(2):388-396. PMC: 7823251. DOI: 10.1210/clinem/dgaa863. View

2.
Gejl M, Gjedde A, Egefjord L, Moller A, Hansen S, Vang K . In Alzheimer's Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial. Front Aging Neurosci. 2016; 8:108. PMC: 4877513. DOI: 10.3389/fnagi.2016.00108. View

3.
Buse J, Nauck M, Forst T, Sheu W, Shenouda S, Heilmann C . Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet. 2012; 381(9861):117-24. DOI: 10.1016/S0140-6736(12)61267-7. View

4.
Mathieu C, Zinman B, Hemmingsson J, Woo V, Colman P, Christiansen E . Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial. Diabetes Care. 2016; 39(10):1702-10. DOI: 10.2337/dc16-0691. View

5.
Lingvay I, Hansen T, Macura S, Marre M, Nauck M, de la Rosa R . Superior weight loss with once-weekly semaglutide versus other glucagon-like peptide-1 receptor agonists is independent of gastrointestinal adverse events. BMJ Open Diabetes Res Care. 2020; 8(2). PMC: 7594204. DOI: 10.1136/bmjdrc-2020-001706. View