Beyond Weight Loss and Glycemic Control: Molecular Mechanisms and Hypothesis-Generating Therapeutic Potential of Incretin-Based Therapies Against Peritoneal Fibrosis in Peritoneal Dialysis.
4 affiliations
- 1Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan.
- 2Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833253, Taiwan.
- 3Division of Nephrology, Kaohsiung Municipal Fong-Shan Hospital, Kaohsiung 83062, Taiwan.
- 4Division of Nephrology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan.
Abstract
Background: Peritoneal dialysis (PD) is an established kidney replacement therapy, but long-term exposure to bioincompatible dialysate, uremic toxins, recurrent peritonitis, glucose degradation products, oxidative stress, and sterile inflammation progressively remodels the peritoneal membrane and contributes to peritoneal fibrosis (PF). This review summarizes the molecular basis of PF in PD and evaluates the therapeutic rationale for incretin-based interventions beyond weight loss and glycemic control. Methods: This narrative review synthesizes mechanistic, translational, and clinically relevant literature on PD-associated PF, with emphasis on DPP-4 biology, GLP-1 receptor agonism, inflammatory and oxidative signaling, angiogenesis, mesothelial-to-mesenchymal transition, glycemic management in PD, and selected author-conducted translational studies interpreted alongside independent evidence. Results: Available evidence supports a model in which DPP-4 activation, altered GLP-1/GLP-1R signaling, TGF-β/Smad3-driven mesothelial transition, NF-κB/MyD88 inflammation, ROS-mediated oxidative stress, angiogenesis, apoptosis, and cytoskeletal remodeling converge to impair peritoneal membrane integrity. DPP-4 inhibition, exendin-4, and dulaglutide attenuated these pathways in experimental models, while GLP-1 receptor agonists have established metabolic benefits in appropriate diabetic and obese populations. Conclusions: Direct clinical evidence that incretin-based therapies prevent or treat peritoneal fibrosis in humans undergoing PD is currently lacking. Therefore, peritoneal membrane protection, reduced ultrafiltration failure, and improved technique survival should be regarded as investigational, hypothesis-generating possibilities that require prospective clinical validation.
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BibTeX
@article{li2026beyond,
title = {{Beyond Weight Loss and Glycemic Control: Molecular Mechanisms and Hypothesis-Generating Therapeutic Potential of Incretin-Based Therapies Against Peritoneal Fibrosis in Peritoneal Dialysis.}},
author = {Yi-Chen Li and Jui-Ting Hsu and Chung-Ming Fu and Ting-Chun Liu and Yueh-Ting Lee and Po-Jung Wu and Lung-Chih Li and Terry Ting-Yu Chiou and Chien-Hua Chiu and Wei-Hung Kuo and Chiang-Chi Huang and Kai-Fan Tsai and Tsuen-Wei Hsu and Wen-Chin Lee and Chien-Te Lee and Chih-Chao Yang},
journal = {Pharmaceuticals (Basel, Switzerland)},
year = {2026},
month = sep,
doi = {10.3390/ph19101502},
url = {https://europepmc.org/article/MED/42943198},
note = {CC BY},
}
RIS
TY - JOUR
TI - Beyond Weight Loss and Glycemic Control: Molecular Mechanisms and Hypothesis-Generating Therapeutic Potential of Incretin-Based Therapies Against Peritoneal Fibrosis in Peritoneal Dialysis.
AU - Yi-Chen Li
AU - Jui-Ting Hsu
AU - Chung-Ming Fu
AU - Ting-Chun Liu
AU - Yueh-Ting Lee
AU - Po-Jung Wu
AU - Lung-Chih Li
AU - Terry Ting-Yu Chiou
AU - Chien-Hua Chiu
AU - Wei-Hung Kuo
AU - Chiang-Chi Huang
AU - Kai-Fan Tsai
AU - Tsuen-Wei Hsu
AU - Wen-Chin Lee
AU - Chien-Te Lee
AU - Chih-Chao Yang
PY - 2026
DA - 2026/09/22
JO - Pharmaceuticals (Basel, Switzerland)
DO - 10.3390/ph19101502
UR - https://europepmc.org/article/MED/42943198
AB - Background: Peritoneal dialysis (PD) is an established kidney replacement therapy, but long-term exposure to bioincompatible dialysate, uremic toxins, recurrent peritonitis, glucose degradation products, oxidative stress, and sterile inflammation progressively remodels the peritoneal membrane and contributes to peritoneal fibrosis (PF). This review summarizes the molecular basis of PF in PD and evaluates the therapeutic rationale for incretin-based interventions beyond weight loss and glycemic control. Methods: This narrative review synthesizes mechanistic, translational, and clinically relevant literature on PD-associated PF, with emphasis on DPP-4 biology, GLP-1 receptor agonism, inflammatory and oxidative signaling, angiogenesis, mesothelial-to-mesenchymal transition, glycemic management in PD, and selected author-conducted translational studies interpreted alongside independent evidence. Results: Available evidence supports a model in which DPP-4 activation, altered GLP-1/GLP-1R signaling, TGF-β/Smad3-driven mesothelial transition, NF-κB/MyD88 inflammation, ROS-mediated oxidative stress, angiogenesis, apoptosis, and cytoskeletal remodeling converge to impair peritoneal membrane integrity. DPP-4 inhibition, exendin-4, and dulaglutide attenuated these pathways in experimental models, while GLP-1 receptor agonists have established metabolic benefits in appropriate diabetic and obese populations. Conclusions: Direct clinical evidence that incretin-based therapies prevent or treat peritoneal fibrosis in humans undergoing PD is currently lacking. Therefore, peritoneal membrane protection, reduced ultrafiltration failure, and improved technique survival should be regarded as investigational, hypothesis-generating possibilities that require prospective clinical validation.
SN - 1424-8247
ER -