How GLP-1 and GIP Work: The Biology Behind Today's Most Important Diabetes Drugs

What the researchers 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.

Why it 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 numbers in context

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 the study worked

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.

Who was studied

Review covering preclinical animal studies and clinical trials in humans with type 2 diabetes

What this study cannot 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.

How to read the evidence

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.

When this study was published

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.

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.

Questions still open

• 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?

Common questions

Read the original research

Biology of incretins: GLP-1 and GIP.

Gastroenterology, 132(6), 2131-57

Citation

Baggio, Laurie L; Drucker, Daniel J. (2007). Biology of incretins: GLP-1 and GIP.. Gastroenterology, 132(6), 2131-57.