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Review
. 2021 Jul 17;10(7):R200-R212.
doi: 10.1530/EC-21-0130.

How glucagon-like peptide 1 receptor agonists work

Christine Rode Andreasen  1   2 , Andreas Andersen  1   2 , Filip Krag Knop  1   2   3   4 , Tina Vilsbøll  1   2   3
Affiliations
Review

How glucagon-like peptide 1 receptor agonists work

Christine Rode Andreasen et al. Endocr Connect. .

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.

Keywords: cardiovascular; diabetes; inflammation; metabolism; obesity.

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Figures

Figure 1
Figure 1
Possible actions of glucagon-like peptide 1 (GLP-1) and the GLP-1 receptor agonists (GLP-1RAs) on various tissue. The applied colour code indicates whether the effect on the target tissue has been observed in preclinical studies (blue boxes), at physiological levels of GLP-1 in clinical studies (green boxes) or after treatment with GLP-1RAs (red boxes) (1, 2). The figure illustrates GLP-1 (7–36) amide.
Figure 2
Figure 2
Results from clinical trials comparing the GLP-1 receptor agonists (GLP-1RAs) head-to-head in phase III trials. Left panels are trials comparing short-acting GLP-1RAs (97). Middle panels are trials comparing a short-acting GLP-1RA with a long-acting GLP-1RA (7, 98, 99, 100). Right panel are trials comparing long-acting GLP-1RAs (101, 102, 103, 104, 105, 106). Asterisk (*) represents significant differences when comparing the GLP-1RAs.
Figure 3
Figure 3
Possible cardiovascular actions of glucagon-like peptide 1 (GLP-1) and GLP-1 receptor agonists (GLP-1RAs).
See this image and copyright information in PMC

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