Therapeutic Effects of GLP-1 Receptor Agonists and DPP-4 Inhibitors in Neuropathic Pain: Mechanisms and Clinical Implications

Glucagon-like peptide-1 (GLP-1) is a peptide hormone secreted by the small intestine upon food intake. GLP-1 enhances insulin secretion, suppresses glucagon release, and promotes satiety, resulting in reduced food consumption and subsequent weight loss. Endogenous GLP-1 has a very short half-life an...

Full description

Saved in:
Bibliographic Details
Main Authors: Yaswanth Kuthati, Venkata Naga Goutham Davuluri, Chih-Shung Wong
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/15/5/622
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849711523601055744
author Yaswanth Kuthati
Venkata Naga Goutham Davuluri
Chih-Shung Wong
author_facet Yaswanth Kuthati
Venkata Naga Goutham Davuluri
Chih-Shung Wong
author_sort Yaswanth Kuthati
collection DOAJ
description Glucagon-like peptide-1 (GLP-1) is a peptide hormone secreted by the small intestine upon food intake. GLP-1 enhances insulin secretion, suppresses glucagon release, and promotes satiety, resulting in reduced food consumption and subsequent weight loss. Endogenous GLP-1 has a very short half-life and is rapidly degraded by the enzyme dipeptidyl-peptidase-IV (DPP-4). To address this limitation, GLP-1 receptor agonists (GLP-1RAs) and DPP-4 inhibitors (DPP-4is) were developed and have demonstrated potency in clinical practice. In recent years, GLP-1RA and DPP4-i therapies are known to have pleiotropic effects, such as a reduction in oxidative stress, autophagy regulation, metabolic reprogramming, enhancement of anti-inflammatory signaling, regulation of gene expression, and being neuroprotective. These effects imply a therapeutic perspective for GLP-1RA and DPP-4i therapies in neuropathic pain treatment. Preclinical and clinical studies increasingly support the hypothesis that these therapies may alleviate neuropathic pain by targeting multiple mechanisms that induce neuropathic pain, such as inflammation, oxidative stress, and mitochondrial dysfunction. This review explores the mechanisms by which GLP-1RAs and DPP-4is alleviate neuropathic pain. It also highlights current advancements in incretin research, focusing on the therapeutic effects of GLP-1RAs and DPP-4-is for neuropathic pain.
format Article
id doaj-art-d642224f3b6c4e4ca8a164ba38b5039c
institution DOAJ
issn 2218-273X
language English
publishDate 2025-04-01
publisher MDPI AG
record_format Article
series Biomolecules
spelling doaj-art-d642224f3b6c4e4ca8a164ba38b5039c2025-08-20T03:14:36ZengMDPI AGBiomolecules2218-273X2025-04-0115562210.3390/biom15050622Therapeutic Effects of GLP-1 Receptor Agonists and DPP-4 Inhibitors in Neuropathic Pain: Mechanisms and Clinical ImplicationsYaswanth Kuthati0Venkata Naga Goutham Davuluri1Chih-Shung Wong2Department of Anesthesiology, Cathay General Hospital, Taipei 10630, TaiwanDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Anesthesiology, Cathay General Hospital, Taipei 10630, TaiwanGlucagon-like peptide-1 (GLP-1) is a peptide hormone secreted by the small intestine upon food intake. GLP-1 enhances insulin secretion, suppresses glucagon release, and promotes satiety, resulting in reduced food consumption and subsequent weight loss. Endogenous GLP-1 has a very short half-life and is rapidly degraded by the enzyme dipeptidyl-peptidase-IV (DPP-4). To address this limitation, GLP-1 receptor agonists (GLP-1RAs) and DPP-4 inhibitors (DPP-4is) were developed and have demonstrated potency in clinical practice. In recent years, GLP-1RA and DPP4-i therapies are known to have pleiotropic effects, such as a reduction in oxidative stress, autophagy regulation, metabolic reprogramming, enhancement of anti-inflammatory signaling, regulation of gene expression, and being neuroprotective. These effects imply a therapeutic perspective for GLP-1RA and DPP-4i therapies in neuropathic pain treatment. Preclinical and clinical studies increasingly support the hypothesis that these therapies may alleviate neuropathic pain by targeting multiple mechanisms that induce neuropathic pain, such as inflammation, oxidative stress, and mitochondrial dysfunction. This review explores the mechanisms by which GLP-1RAs and DPP-4is alleviate neuropathic pain. It also highlights current advancements in incretin research, focusing on the therapeutic effects of GLP-1RAs and DPP-4-is for neuropathic pain.https://www.mdpi.com/2218-273X/15/5/622glucagon-like peptide-1dipeptidyl-peptidase-IV inhibitorsneuropathic painoxidative stressinflammation
spellingShingle Yaswanth Kuthati
Venkata Naga Goutham Davuluri
Chih-Shung Wong
Therapeutic Effects of GLP-1 Receptor Agonists and DPP-4 Inhibitors in Neuropathic Pain: Mechanisms and Clinical Implications
Biomolecules
glucagon-like peptide-1
dipeptidyl-peptidase-IV inhibitors
neuropathic pain
oxidative stress
inflammation
title Therapeutic Effects of GLP-1 Receptor Agonists and DPP-4 Inhibitors in Neuropathic Pain: Mechanisms and Clinical Implications
title_full Therapeutic Effects of GLP-1 Receptor Agonists and DPP-4 Inhibitors in Neuropathic Pain: Mechanisms and Clinical Implications
title_fullStr Therapeutic Effects of GLP-1 Receptor Agonists and DPP-4 Inhibitors in Neuropathic Pain: Mechanisms and Clinical Implications
title_full_unstemmed Therapeutic Effects of GLP-1 Receptor Agonists and DPP-4 Inhibitors in Neuropathic Pain: Mechanisms and Clinical Implications
title_short Therapeutic Effects of GLP-1 Receptor Agonists and DPP-4 Inhibitors in Neuropathic Pain: Mechanisms and Clinical Implications
title_sort therapeutic effects of glp 1 receptor agonists and dpp 4 inhibitors in neuropathic pain mechanisms and clinical implications
topic glucagon-like peptide-1
dipeptidyl-peptidase-IV inhibitors
neuropathic pain
oxidative stress
inflammation
url https://www.mdpi.com/2218-273X/15/5/622
work_keys_str_mv AT yaswanthkuthati therapeuticeffectsofglp1receptoragonistsanddpp4inhibitorsinneuropathicpainmechanismsandclinicalimplications
AT venkatanagagouthamdavuluri therapeuticeffectsofglp1receptoragonistsanddpp4inhibitorsinneuropathicpainmechanismsandclinicalimplications
AT chihshungwong therapeuticeffectsofglp1receptoragonistsanddpp4inhibitorsinneuropathicpainmechanismsandclinicalimplications