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REVIEW article

Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1431292

Mechanisms of Action and Therapeutic Applications of GLP-1 and Dual GIP/GLP-1 Receptor Agonists

Provisionally accepted
Qiyuan K. Liu Qiyuan K. Liu 1,2*
  • 1 MedStar Health, Columbia, United States
  • 2 MedStar Montgomery Medical Center, Olney, United States

The final, formatted version of the article will be published soon.

    Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are two incretins that bind to their respective receptors and activate the downstream signaling in a variety of tissues and organs. Both GIP and GLP-1 play a role in regulating food intake by stimulating neurons in the brain's satiety center. They also stimulate insulin secretion in pancreatic b-cells, but their effects on the glucagon production in pancreatic a-cells differ, with GIP have a glucagonotropic effect during hypoglycemia and GLP-1 exhibiting glucagonostatic effect during hyperglycemia. Additionally, GIP directly stimulates lipogenesis, while GLP-1 indirectly promotes lipolysis, collectively maintaining healthy adipocytes, reducing the ectopic fat distribution, increasing production and secretion of adiponectin from adipocytes. Together, these two incretins contribute to metabolic homeostasis, preventing both hyperglycemia and hypoglycemia, mitigating dyslipidemia, and reducing the risk of cardiovascular diseases in individuals with type 2 diabetes and obesity. Several GLP-1 and dual GIP/GLP-1 receptor agonists have been developed to harness these pharmacological effects in the treatment of type 2 diabetes with some demonstrating robust effectiveness in weight management and prevention of cardiovascular diseases. Elucidating the underlying cellular and molecular mechanisms could potentially usher the development of new generations of incretin analogues with enhanced efficacy and fewer adverse effects. The treatment guidelines are evolving based on clinical trial outcomes, shaping the management of the metabolic and cardiovascular diseases. Number of words: 11,580 Number of figures: 2 Number of tables: 2 Number of supplemental tables: 1 10 µg twice daily injection Yes 1 (2005) No No No No Exenatide ER (Bydureonâ; Amylin and Eli Lilly) 2 mg once weekly injection Yes (2012) No No No No Lixisenatide 2 (Adlyxinâ; Sanofi) 20 µg once daily injection Yes (2016) No No No No Albiglutide (Tanzeumâ; GlaxoSmithKline) 3 50 mg once weekly injection Yes (2014) No No No No Dulaglutide (TrulicityÒ; Eli Lilly) 4.5 mg once weekly injection

    Keywords: GIP, GLP-1, GLP-1RA, tirzepatide, diabetes, Obesity, cardiovascular disease

    Received: 11 May 2024; Accepted: 08 Jul 2024.

    Copyright: © 2024 Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Qiyuan K. Liu, MedStar Health, Columbia, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.