Page 55 - GTM-4-1

Global Translational Medicine

PERSPECTIVE ARTICLE
State-of-the-art perspective: Advances in

incretin-based therapy targeting progression of
diabetes and cardiovascular-kidney-metabolic

syndrome

Samar A. Nasser 1 , Anuhya V. Pulapaka 2 , Shaveta Gupta 2 , and
2
Keith C. Ferdinand *
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
(This article belongs to the Special Issue: Convergence of Cardiorenal Metabolic Disease: From
Epigenetics to End Stage)

Abstract

The incretin system is targeted in the treatment of type 2 diabetes mellitus (T2DM) and
*Corresponding author: cardiovascular-kidney-metabolic (CKM) conditions. Increasingly, incretin hormones
Keith C. Ferdinand (i.e., gut peptides that enhance glucose-stimulated insulin secretion) reduce blood
(kferdina@tulane.edu)
glucose levels, consequently alleviating CKM syndrome. Specifically, glucagon-like
Citation: Nasser SA, Pulapaka AV, peptide 1 (GLP-1) demonstrated glucose-lowering effects, delayed gastric emptying,
Gupta S, Ferdinand KC.
State-of-the-art perspective: decreased glucagon secretion, and weight loss. An investigational medication,
Advances in incretin-based retatrutide, interacts as a tri-agonist with glucose-dependent insulinotropic
therapy targeting progression polypeptide (GIP), GLP-1, and the glucagon receptor. Contemporary data indicate
of diabetes and cardiovascular- that early intervention, targeting not only the GLP-1 receptor but also the GIP and
kidney-metabolic syndrome. Global
Transl Med. 2025:4(1):47-55. glucagon receptors, are forthcoming therapeutics affecting T2DM in earlier phases
doi: 10.36922/gtm.4405 and CKM outcomes, demonstrating the advances in tri-agonists versus only GLP-1.
Received: August 1, 2024 Notably, endogenous levels of gut incretin hormones shift as pre-diabetes progresses
to diabetes or regresses to normoglycemia. The present perspective provides a
1st revised: September 4, 2024
review of incretin therapy and its prospects in hindering the progression of T2DM
2nd revised: September 18, 2024 and CKM syndrome.
Accepted: October 8, 2024
Published online: December 31, Keywords: Pre-diabetes; Type 2 diabetes; Cardiovascular-kidney-metabolic syndrome;
2024 Incretin mimetics; Obesity
Copyright: © 2024 Author(s).
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution, 1. Introduction
and reproduction in any medium,
provided the original work is Incretin-based therapies have revolutionized the treatment of type 2 diabetes mellitus
properly cited. (T2DM) and cardiovascular-kidney-metabolic (CKM) conditions. These therapies
Publisher’s Note: AccScience target the incretin system, which involves gut peptides that enhance glucose-
Publishing remains neutral with stimulated insulin secretion, thereby reducing blood glucose levels and alleviating
regard to jurisdictional claims in 20,21
published maps and institutional CKM syndrome. Glucagon-like peptide-1 (GLP-1) has emerged as a key player in
affiliations. this therapeutic approach. GLP-1 receptor agonists demonstrate multiple beneficial

Volume 4 Issue 1 (2025) 47 doi: 10.36922/gtm.4405