Proglucagon-Derived Peptides: The Complete Family Behind GLP-1, GLP-2, and Glucagon Therapies
Comprehensive review of all proglucagon-derived peptides — glucagon, GLP-1, GLP-2, oxyntomodulin, glicentin, and GRPP — covering their biology and therapeutic applications from diabetes to obesity to short bowel syndrome.
Quick Facts
What This Study Found
Proglucagon-derived peptide family includes glucagon, GLP-1, GLP-2, oxyntomodulin, glicentin, and GRPP. Each has distinct biology and therapeutic applications. GLP-1 dominates current therapeutics, while oxyntomodulin and glucagon combinations are emerging.
Key Numbers
Covers glucagon, GLP-1, GLP-2, OXM, glicentin, GRPP; approved drugs include semaglutide, liraglutide, exenatide, dulaglutide, teduglutide
How They Did This
Comprehensive narrative review of all proglucagon-derived peptides, their processing, biology, physiological functions, and therapeutic applications.
Why This Research Matters
Understanding the full proglucagon family explains why multi-receptor agonists (like tirzepatide and cotadutide) are so effective — they harness multiple peptides from the same natural system for synergistic metabolic effects.
The Bigger Picture
The proglucagon gene is arguably the most therapeutically productive gene in human biology. Understanding how nature processes one protein into multiple hormones with complementary functions has directly inspired the multi-receptor drug design strategy dominating metabolic medicine.
What This Study Doesn't Tell Us
Broad review covering extensive biology. Some peptides (glicentin, GRPP) have poorly understood functions. Therapeutic applications are at different stages of development.
Questions This Raises
- ?Will triple agonists (GLP-1/GIP/glucagon) dominate future obesity treatment?
- ?What are the physiological roles of the less-studied PGDPs like glicentin and GRPP?
- ?Could targeting all proglucagon peptides simultaneously provide optimal metabolic control?
Trust & Context
- Key Stat:
- 1 gene, 6+ medicines One proglucagon gene produces at least 6 bioactive peptides, several of which are now FDA-approved drugs or clinical candidates — the most therapeutically productive gene family in medicine
- Evidence Grade:
- Not applicable (comprehensive review). Based on decades of established biology and clinical evidence.
- Study Age:
- Published 2021. Multi-receptor proglucagon-based therapies continue advancing rapidly.
- Original Title:
- Proglucagon-Derived Peptides as Therapeutics.
- Published In:
- Frontiers in endocrinology, 12, 689678 (2021)
- Authors:
- Lafferty, Ryan A(3), O'Harte, Finbarr P M, Irwin, Nigel(7), Gault, Victor A, Flatt, Peter R
- Database ID:
- RPEP-05524
Evidence Hierarchy
Summarizes existing research on a topic.
What do these levels mean? →Frequently Asked Questions
Are GLP-1 and glucagon related?
Yes — they come from the same precursor protein (proglucagon). GLP-1 lowers blood sugar and suppresses appetite, while glucagon raises blood sugar. Paradoxically, combining both in drugs like cotadutide may produce superior metabolic benefits through complementary mechanisms.
How many drugs come from this one gene?
The proglucagon gene has produced multiple approved drugs: GLP-1 analogues (semaglutide, liraglutide, exenatide, dulaglutide for diabetes/obesity), GLP-2 analogues (teduglutide for short bowel syndrome), and glucagon (for hypoglycemia rescue). More are in development.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-05524APA
Lafferty, Ryan A; O'Harte, Finbarr P M; Irwin, Nigel; Gault, Victor A; Flatt, Peter R. (2021). Proglucagon-Derived Peptides as Therapeutics.. Frontiers in endocrinology, 12, 689678. https://doi.org/10.3389/fendo.2021.689678
MLA
Lafferty, Ryan A, et al. "Proglucagon-Derived Peptides as Therapeutics.." Frontiers in endocrinology, 2021. https://doi.org/10.3389/fendo.2021.689678
RethinkPeptides
RethinkPeptides Research Database. "Proglucagon-Derived Peptides as Therapeutics." RPEP-05524. Retrieved from https://rethinkpeptides.com/research/lafferty-2021-proglucagonderived-peptides-as-therapeutics
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.