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PERSPECTIVE ARTICLE

State-of-the-art perspective: Advances in incretin-based therapy targeting progression of diabetes and cardiovascular-kidney-metabolic syndrome

Samar A. Nasser1 ,  Anuhya V. Pulapaka2 ,  Shaveta Gupta2 ,  Keith C. Ferdinand2*
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1 Department of Clinical Research and Leadership, School of Medicine and Health Sciences, The George Washington University, Washington, D.C., United States of America
2 Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America
Global Translational Medicine, 4405 https://doi.org/10.36922/gtm.4405
Submitted: 1 August 2024 | Accepted: 8 October 2024 | Published: 31 December 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The incretin system is targeted in the treatment of type 2 diabetes mellitus (T2DM) and cardiovascular-kidney-metabolic (CKM) conditions. Increasingly, incretin hormones (i.e., gut peptides that enhance glucose-stimulated insulin secretion) reduce blood glucose levels, consequently alleviating CKM syndrome. Specifically, glucagon-like peptide 1 (GLP-1) demonstrated glucose-lowering effects, delayed gastric emptying, decreased glucagon secretion, and weight loss. An investigational medication, retatrutide, interacts as a tri-agonist with glucose-dependent insulinotropic polypeptide (GIP), GLP-1, and the glucagon receptor. Contemporary data indicate that early intervention, targeting not only the GLP-1 receptor but also the GIP and glucagon receptors, are forthcoming therapeutics affecting T2DM in earlier phases and CKM outcomes, demonstrating the advances in tri-agonists versus only GLP-1. Notably, endogenous levels of gut incretin hormones shift as pre-diabetes progresses to diabetes or regresses to normoglycemia. The present perspective provides a review of incretin therapy and its prospects in hindering the progression of T2DM and CKM syndrome.

Keywords
Pre-diabetes
Type 2 diabetes
Cardiovascular-kidney-metabolic syndrome
Incretin mimetics
Obesity
Funding
None.
Conflict of interest
The authors declare no conflicts of interest.
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Global Translational Medicine, Electronic ISSN: 2811-0021 Print ISSN: 3060-8600, Published by AccScience Publishing
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