How GLP-1 and GIP Work: The Biology Behind Today's Most Important Diabetes Drugs
GLP-1 and GIP are gut hormones released after meals that boost insulin, protect pancreatic cells, and laid the groundwork for modern diabetes and weight-loss medications.
Quick Facts
What This Study Found
GLP-1 and GIP are both released within minutes of eating and help the body process nutrients by stimulating insulin release from pancreatic beta cells. Both peptides promote beta-cell growth and protect these cells from dying.
However, the two peptides differ in important ways. GIP promotes fat storage and strengthens bones by stimulating bone-building cells. GLP-1, on the other hand, slows stomach emptying, suppresses glucagon (a sugar-raising hormone), promotes feelings of fullness, and is associated with weight loss.
Both peptides are rapidly broken down by the enzyme DPP-4, which led to two classes of diabetes drugs: degradation-resistant GLP-1 receptor agonists and DPP-4 inhibitors. These therapies lower HbA1c without causing weight gain in people with type 2 diabetes.
Key Numbers
Both incretins secreted within minutes of eating · DPP-4 rapidly degrades both GLP-1 and GIP · GLP-1 agonists and DPP-4 inhibitors lower HbA1c without weight gain
How They Did This
Comprehensive narrative review of the published scientific literature on GLP-1 and GIP biology, with emphasis on recent advances in understanding incretin synthesis, secretion, biological actions, receptor signaling, and therapeutic applications.
Why This Research Matters
This review laid out the scientific foundation for the entire incretin-based drug class that would go on to become the most important development in diabetes and obesity treatment. Understanding how GLP-1 and GIP work differently — and how they complement each other — is essential to grasping why newer dual-agonist drugs like tirzepatide target both pathways simultaneously.
The Bigger Picture
This 2007 review is one of the foundational papers that explained how incretin hormones work — knowledge that directly enabled the development of blockbuster drugs like semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound). Understanding the distinct roles of GLP-1 and GIP helps explain why dual-agonist drugs that target both receptors simultaneously may produce even greater metabolic benefits than GLP-1-only drugs.
What This Study Doesn't Tell Us
As a narrative review from 2007, it predates the clinical success of semaglutide, tirzepatide, and other modern incretin therapies. It cannot account for the large-scale cardiovascular and weight-loss outcomes data that emerged in subsequent years. The review also could not anticipate the resurgence of interest in GIP receptor agonism as a therapeutic strategy.
Questions This Raises
- ?Could GIP receptor agonism add therapeutic benefit on top of GLP-1 agonism for weight loss and diabetes?
- ?What are the long-term effects of sustained incretin receptor activation on pancreatic beta cells?
- ?Can the bone-building effects of GIP be harnessed as a standalone treatment for osteoporosis?
Trust & Context
- Key Stat:
- 2 gut hormones GLP-1 and GIP are both released within minutes of eating, but have very different effects — GLP-1 suppresses appetite and promotes weight loss, while GIP promotes fat storage and bone growth
- Evidence Grade:
- This is a comprehensive narrative review published in Gastroenterology, a top-tier journal, by Daniel Drucker — one of the world's foremost authorities on incretin biology. It synthesizes a large body of preclinical and clinical evidence, earning a high evidence grade for a review.
- Study Age:
- Published in 2007, this review predates the clinical breakthroughs of semaglutide and tirzepatide but remains highly relevant as the foundational explanation of incretin biology that made those drugs possible.
- Original Title:
- Biology of incretins: GLP-1 and GIP.
- Published In:
- Gastroenterology, 132(6), 2131-57 (2007)
- Authors:
- Baggio, Laurie L(3), Drucker, Daniel J(11)
- Database ID:
- RPEP-01210
Evidence Hierarchy
Summarizes existing research on a topic.
What do these levels mean? →Frequently Asked Questions
What is the difference between GLP-1 and GIP?
Both are gut hormones that stimulate insulin release after eating, but they differ in other effects. GLP-1 slows stomach emptying, suppresses appetite, and promotes weight loss. GIP promotes fat storage in adipose tissue and stimulates bone formation. Modern drugs like tirzepatide target both hormones simultaneously.
Why do GLP-1 drugs work but natural GLP-1 doesn't last long enough?
Your body's natural GLP-1 is broken down within minutes by an enzyme called DPP-4. Drug developers solved this by creating GLP-1 receptor agonists that resist DPP-4 degradation, allowing them to stay active for days or even a week — which is why semaglutide only needs a once-weekly injection.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-01210APA
Baggio, Laurie L; Drucker, Daniel J. (2007). Biology of incretins: GLP-1 and GIP.. Gastroenterology, 132(6), 2131-57.
MLA
Baggio, Laurie L, et al. "Biology of incretins: GLP-1 and GIP.." Gastroenterology, 2007.
RethinkPeptides
RethinkPeptides Research Database. "Biology of incretins: GLP-1 and GIP." RPEP-01210. Retrieved from https://rethinkpeptides.com/research/baggio-2007-biology-of-incretins-glp1
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.