How GLP medicines began: an illustrated history

The earlier hormone story

GLP medicines grew from decades of work on how the gut and pancreas communicate. Their history includes identifying a signal, finding its biologically active form, understanding what it does and developing molecules that can become practical medicines. Different researchers solved different parts of that chain.

The famous Toronto insulin story provides useful context, but it is a separate hormone discovery. The FDA’s insulin history places Banting and Best’s experiments in 1921 and early clinical work in January 1922, with Collip’s purification work part of the wider effort. The photograph below belongs to that earlier chapter; it is not a picture of GLP’s discovery.

The gut-to-pancreas clue

By the 1960s, experiments showed that glucose taken by mouth could produce a different insulin response from glucose delivered into a vein. The gut was doing more than delivering nutrients: chemical signals helped connect eating with the pancreas’s response. That observation is part of what researchers call the incretin effect.

This was an important question before the current medicine names existed. “GLP-1” is a hormone and receptor term, while Ozempic is a product name and tirzepatide is a molecule name. Keeping that vocabulary straight makes the history—and today’s headlines—easier to follow.

1. 1964Studies of oral versus intravenous glucose provide evidence for gut signals that influence insulin release.
2. 1982Anglerfish glucagon-gene research points to related peptide sequences in a larger precursor.
3. The 1980sPeptide chemistry, cell experiments and physiology establish the active GLP-1 signal and its glucose-dependent insulin effects.

The Lasker Foundation’s discovery account describes the oral-glucose work and the gene-cloning discoveries. These milestones represent different experiments, rather than a single day on which a modern drug was invented.

Why an anglerfish mattered

Researchers investigating glucagon used the anglerfish because its endocrine anatomy offered practical advantages for studying hormone genes. The resulting work helped reveal that a larger precursor could contain instructions for several related peptides. Knowing a sequence was only one step: scientists still needed to identify how it was processed and which form was active.

Joel Habener’s gene work, Svetlana Mojsov’s peptide synthesis and identification, experiments with Gordon Weir, Daniel Drucker’s cell work and Jens Juul Holst’s physiology research contributed different pieces. The 2017 JCI history by Drucker, Habener and Holst places those lines of work in a wider collaborative story.

In 2024, the Lasker clinical award recognized Habener, Mojsov and Lotte Bjerre Knudsen. Its account distinguishes identifying the active signal from Knudsen’s later work developing long-acting analogues. Recognition of particular contributors should not erase the other experiments and teams that made translation possible.

From a signal to a practical medicine

A useful physiological signal does not automatically make a convenient treatment. Researchers had to study duration of action, molecular design and ways of giving a medicine reliably. The history therefore includes both basic biology and development work.

Research on exendin-4 from the Gila monster offered another important route. It helped lead to synthetic exenatide, approved in the United States for type 2 diabetes in 2005. Modern semaglutide and tirzepatide are not medicines extracted from lizard venom; different molecules have different development histories. The NIDDK discovery account explains the fish and lizard connections.

How a diabetes story became a weight-management story

Work on GLP-1 did not stop at insulin secretion. Research moved from observations in animals to studies of fullness and food intake in people, followed by weight-related findings in diabetes and obesity research. Drucker’s 2024 JCI perspective explains this progression and distinguishes normal hormone signaling from the effects of pharmacological receptor activation.

That distinction matters. A medicine’s action over time, the studied population and the dose regimen all need their own evidence.

1. 2005Synthetic exenatide enters US type 2 diabetes treatment.
2. December 2014Liraglutide as Saxenda receives a US weight-management approval.
3. June 2021The FDA approves Wegovy injection for chronic weight management in specified adults.
4. November 2023The FDA approves Zepbound for chronic weight management, introducing tirzepatide’s dual GIP/GLP-1 action to that indication.

These are initial US approval milestones. Later expanded indications and new presentations have their own dates and product labels; an older news release is not a complete description of a medicine today.

The story is still developing

By October 2026, current US labels include both injection and tablet presentations of Ozempic and Wegovy. Foundayo, containing orforglipron, received FDA approval in April 2026. These changes show why an article should identify a product and presentation precisely rather than assume every familiar brand still means one weekly injection.

Retatrutide belongs to the research chapter. Lilly describes it as an investigational triple GIP, GLP-1 and glucagon receptor agonist, without regulatory approval. A trial announcement, a regulator’s decision and a pharmacy product are different milestones. Our guide to the names maps those distinctions.