Proglucagon-derived peptides: human physiology and therapeutic potential
Lærke S Gasbjerg1,2, Casper K Nielsen1,3, Malte P Suppli1
1Center for Clinical Metabolic Research, Herlev and Gentofte University Hospital, Copenhagen, Denmark.
Physiological Reviews
|July 28, 2025
Summary
Proglucagon-derived peptides like GLP-1 are key hormones regulating metabolism and appetite. They offer vital therapeutic applications for diabetes, obesity, and short bowel syndrome.
Area of Science:
- Endocrinology and Metabolism
- Gastroenterology
- Pharmacology
Background:
- Proglucagon-derived peptides (PGDPs) are crucial hormones regulating glucose, lipid, and protein metabolism, appetite, and gastrointestinal function.
- PGDPs, including glucagon, glucagon-like peptide 1 (GLP-1), glucagon-like peptide 2 (GLP-2), and oxyntomodulin, act via distinct G protein-coupled receptors.
- These peptides play significant roles in endocrine, neuroendocrine, and metabolic processes, emerging as central therapeutic targets.
Purpose of the Study:
- To review the human physiology of PGDPs.
- To explore the involvement of PGDPs in pathophysiology.
- To discuss current and future therapeutic applications of PGDPs and related receptor agonists.
Main Methods:
- Clinical review of existing literature on proglucagon-derived peptides.
- Analysis of physiological roles, pathophysiological involvement, and therapeutic applications.
- Discussion of advancements in mono- and multi-receptor agonists and future perspectives.
Main Results:
- Glucagon is established for hypoglycemia treatment.
- GLP-1 receptor agonists have transformed type 2 diabetes and obesity management with glucose-lowering, appetite-suppressing, and cardioprotective effects.
- GLP-2 analogues provide targeted therapy for short bowel syndrome.
Conclusions:
- PGDPs are vital regulators of human physiology with significant therapeutic potential.
- Advancements in receptor agonists offer improved treatment strategies for metabolic and gastrointestinal diseases.
- Future research holds promise for novel indications and combination therapies involving PGDPs.
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