A History of Peptide Drugs: From Insulin to the GLP-1 Era

Published September 2026 · Patriot Labs Research Team · ~18 min read

The short answer

The history of peptide drugs begins with insulin, isolated in 1921 and first given to a patient in 1922, and runs through the invention of peptide synthesis in the 1960s, the first genetically engineered drug in 1982, and the GLP-1 medicines of the last two decades. Along the way peptides went from being harvested out of animal glands to being built atom by atom or grown in engineered microbes.

Three threads run through the whole story. The first is discovery — working out what the body’s own signalling peptides are and what they are made of. The second is chemistry and biotechnology — learning to determine a peptide’s sequence, then to build it or grow it reliably at scale. The third is regulation and industry — the approvals, patents and factories that turned individual molecules into products. This guide follows those threads in roughly chronological order, treating each milestone as a matter of scientific and regulatory record rather than a statement about any effect in a person.

Insulin: the first peptide drug (1921–1923)

Insulin is where the history of peptide drugs starts, because it was the first peptide hormone isolated and put to therapeutic use. Its discovery is also the moment a molecule made inside the body became something that could be manufactured and supplied.

In the summer of 1921, at the University of Toronto, the surgeon Frederick Banting and the medical student Charles Best — working in the laboratory of the physiologist J. J. R. Macleod, and later joined by the biochemist James Collip, who purified the extract — obtained a pancreatic extract that lowered blood sugar in animals. On 11 January 1922 a 14-year-old patient with type 1 diabetes, Leonard Thompson, received the first injection; an early, less pure preparation produced little effect, but a purified extract given days later did, and Thompson’s case became the proof that the extract worked.^[1][2] The 1923 Nobel Prize in Physiology or Medicine was awarded to Banting and Macleod “for the discovery of insulin,” and Banting and Best famously assigned the patent to the university for a token sum so that the discovery could be developed widely.^[3]

For the next six decades, the answer to “where does insulin come from” was the slaughterhouse: commercial insulin was extracted from the pancreases of cattle and pigs. That tied supply to the meatpacking industry and meant patients received an animal sequence rather than the human one. The scientific and industrial problem that occupied the rest of the century — how to know a peptide’s exact structure and how to make the human version to order — grew directly out of insulin’s success.

Reading and building the chain (1950s–1960s)

Two mid-century breakthroughs turned peptides from substances that could only be extracted into molecules that could be read and written: Frederick Sanger worked out insulin’s exact amino-acid sequence, and Vincent du Vigneaud and then R. B. Merrifield showed that peptide hormones could be built by chemistry rather than harvested.

Sanger, at the University of Cambridge, determined the complete amino-acid sequence of insulin over the early 1950s, showing for the first time that a protein has a single, defined sequence. The work earned him the 1958 Nobel Prize in Chemistry and established that peptides and proteins are exact chemical entities, not vaguely defined mixtures.^[4] Knowing the sequence was the precondition for everything that followed: a molecule cannot be synthesised or engineered until its structure is known.

In 1953 Vincent du Vigneaud reported the laboratory synthesis of oxytocin, a nine-amino-acid pituitary hormone — the first time a polypeptide hormone had been chemically synthesised and shown to match the natural material. He received the 1955 Nobel Prize in Chemistry for the achievement.^[5] It proved that a biologically active peptide could be assembled from scratch, but the solution-phase methods of the day were slow and demanding.

The decisive step came in 1963, when R. Bruce Merrifield at the Rockefeller Institute published solid-phase peptide synthesis (SPPS). Instead of building a peptide in solution, SPPS anchors the growing chain to an insoluble resin bead and adds one protected amino acid at a time, washing away excess reagents at each step; the finished peptide is cleaved from the resin at the end.^[6] The method was fast, reproducible and, before long, automatable, and it is still the route behind the great majority of synthetic peptides. Merrifield received the 1984 Nobel Prize in Chemistry for it.^[7] The mechanics of SPPS and its modern industrial forms are set out in How Peptides Are Made.

The recombinant revolution (1978–1982)

The single biggest industrial shift in the history of peptide drugs was the move from extraction to recombinant production, and insulin was again the pivot. Recombinant human insulin, approved in 1982, was the first genetically engineered product cleared for use in medicine.

In 1978 scientists at the young biotechnology company Genentech, working with the City of Hope, expressed human insulin in bacteria carrying chemically synthesised genes; a 1979 paper in the Proceedings of the National Academy of Sciences reported the expression in Escherichia coli of chemically synthesized genes for human insulin.^[8] Genentech licensed the technology to Eli Lilly, and the resulting product, Humulin, was approved by the FDA in 1982 — the first recombinant DNA drug on the market anywhere.^[9][10] For the first time, the human sequence could be made in unlimited quantity without depending on animal pancreas, and the biotechnology industry had its founding commercial proof.

Recombinant production suits longer chains and proteins, which are difficult to build by pure chemistry; chemical synthesis suits shorter and chemically modified peptides. The two routes have coexisted ever since, and the trade-offs between them — length limits, non-natural amino acids, impurity profiles — are compared in Recombinant vs Synthetic Peptides.

The analogue era (1980s–1990s)

Once sequences could be read and peptides built to order, chemists stopped copying nature exactly and began designing analogues — peptides deliberately altered to resist breakdown or to act more selectively. The 1980s and 1990s brought a wave of these, and several remain reference points in endocrinology and oncology.

The gonadotropin-releasing hormone (GnRH) analogues were among the most important. Leuprolide, a synthetic GnRH agonist first cleared by the FDA in the mid-1980s, was engineered from the natural ten-amino-acid hormone with substitutions that made it far longer-lasting, and it was later reformulated as long-acting depot injections; its regulatory development is reviewed in the clinical literature.^[11] Around the same period, octreotide, a synthetic eight-amino-acid analogue of the hormone somatostatin, was approved in 1988 and became a mainstay of the peptide toolkit; its much greater stability than the natural hormone is precisely what made it useful as a drug.^[12] Analogues of vasopressin, such as desmopressin, followed the same design logic of modifying a natural peptide for stability and selectivity.

The lesson of the analogue era is a recurring theme in peptide science: the natural molecule is often the starting point, not the drug. Modifications that extend a peptide’s working life — changes to the backbone, non-natural amino acids, added chemical groups — are what make a fragile signalling molecule into something manufacturable and shelf-stable. Those strategies are the subject of Peptide Half-Life Extension.

Peptides for hard targets (2000s)

By the 2000s, chemistry had advanced far enough to make peptides that would once have been considered impossible — very long synthetic chains, and molecules copied from exotic natural sources. Two approvals from the early 2000s show how far the field had come.

Enfuvirtide (Fuzeon), approved by the FDA in 2003 as an HIV entry inhibitor, is a synthetic peptide of 36 amino acids — at the time one of the largest peptides ever made by chemical synthesis at commercial scale, and a demonstration that SPPS could be pushed to lengths previously thought impractical.^[13] Its manufacture required a very long sequence of chemical steps and became a landmark in large-scale peptide production. The following year, ziconotide (Prialt), approved in 2004, took a different route: it is a synthetic copy of a peptide toxin from the venom of a marine cone snail, one of several drugs that trace their origins to venom peptides.^[14]

These approvals mattered less for their individual sequences than for what they proved about the platform: that a peptide could be a viable answer to a target that small molecules could not reach, and that the manufacturing methods had matured enough to make even difficult peptides reliably. That confidence set the stage for the class that would make peptides famous.

The GLP-1 story (1992–today)

The GLP-1 receptor agonists are the most commercially significant peptide drugs in history, and their story begins, improbably, with a lizard. The line runs from a venom peptide identified in 1992 to a class of medicines that reshaped the pharmaceutical market in the 2020s.

Glucagon-like peptide-1 (GLP-1) is a natural gut hormone, but the natural peptide breaks down in the body within minutes, which made it useless as a drug on its own. The breakthrough came from exendin-4, a peptide found in the venom of the Gila monster (Heloderma suspectum) and characterised in 1992, which acts at the GLP-1 receptor but resists rapid breakdown.^[15] A synthetic version, exenatide, was approved by the FDA as Byetta on 28 April 2005 — the first GLP-1 receptor agonist to reach the market.^[16]

What followed was a steady sequence of engineered analogues designed to last longer and be given less often. Liraglutide, modified with a fatty-acid chain that binds it to albumin, was approved as Victoza on 25 January 2010, and later, under the name Saxenda, for chronic weight management on 23 December 2014.^[17][18] Semaglutide, engineered to be longer-acting, was approved as Ozempic on 5 December 2017, as an oral tablet under the name Rybelsus — the first oral GLP-1 — on 20 September 2019, and for chronic weight management as Wegovy on 4 June 2021.^[19][20][21]

The most recent step combined two receptors in one molecule. Tirzepatide, a dual GIP and GLP-1 receptor agonist, was approved as Mounjaro on 13 May 2022 — described by its manufacturer as the first and only GIP/GLP-1 receptor agonist of its kind — and as Zepbound for chronic weight management on 8 November 2023.^[22][23] Triple-receptor agonists such as retatrutide have since been studied in clinical trials.^[24] The enormous demand for these medicines also set off the largest build-out of peptide-manufacturing capacity on record, a story told in Where Are Peptides Made?

A timeline of peptide-drug milestones

The table below gathers the milestones covered above into one view. Dates are of discovery, publication, award or regulatory approval as recorded in the cited sources; they mark events in the scientific and regulatory record, not claims about outcomes.

The GLP-1 era alone produced a dense run of approvals in under two decades, summarised below.

Where peptide drugs stand today

A century after insulin, peptides are an established and fast-growing drug class rather than a niche. Published reviews put the number of therapeutic peptides on the market at roughly 80 worldwide, with a few hundred more in clinical development and many more in preclinical work.

A 2021 review in Nature Reviews Drug Discovery traced how peptide drug discovery broadened from natural hormones toward engineered and computationally designed molecules,^[25] and a 2023 review counted roughly 80 therapeutic peptides on the market, with about 200 in clinical phases and several hundred more in advanced preclinical stages, and noted that the peptide market has been growing faster than the pharmaceutical market as a whole.^[26] The exact count depends on where the boundary between a large peptide and a small protein is drawn, which is one reason different sources give slightly different totals; the distinction between a peptide, a drug and a biologic is examined in Peptide vs Drug vs Biologic.

The direction of travel is consistent across those reviews: toward longer-acting molecules, oral formulations that were long thought impossible for peptides, and multi-target designs such as the dual and triple receptor agonists. Each of those is a continuation of the same century-long project — taking a fragile natural signal and engineering it into something that can be made, stored and supplied.

Approved drug vs research compound

A crucial distinction runs underneath this entire history: an approved peptide drug and a research-grade peptide that shares its name are not the same thing. The history above is a history of medicines — products that went through regulatory review and are manufactured under inspected quality systems.

A research compound sold under the same name as an approved drug has not been through that review, is made to a supplier’s own specification for laboratory use, and is not the approved medicine. “Research grade” is not a regulatory standard, and a shared sequence does not make a research vial into the drug it is named after. For research material, what can be verified is not an approval but the documentation for a specific lot — identity and purity established by testing, recorded on a certificate of analysis. What that certificate does and does not prove is covered in Understanding Peptide COA Testing, and how to evaluate a supplier in How to Buy Research Peptides. For reference, Patriot Labs is a first-responder-owned, US-based company; every batch it sells is tested by an independent US laboratory by HPLC and mass spectrometry, and the certificate of analysis is published on the product page.

What this guide does not establish

This is a history of the science and the industry, and it deliberately stops short of several things.

• It makes no claim about what any compound does in a person or animal. Approvals and indications are described as regulatory facts of record, not as endorsements or statements of effect.
• It is not medical advice and does not describe how to use anything. No dosing, protocol or method of administration is given or implied.
• Dates reflect the cited sources. Discovery is a process rather than a single moment, so “discovery” years mark the events historians and the awarding bodies settled on, and different sources sometimes date the same event a year apart.
• The list of milestones is selective. Many important peptide drugs — calcitonin, desmopressin, the many other analogues — are mentioned only in passing or not at all; the aim is the shape of the history, not a complete catalogue.
• Approved drugs are not the same as research compounds. Nothing here describes, recommends or characterises any research-grade product, which is not the approved medicine that shares its name.

Frequently asked questions

What was the first peptide drug?

Insulin. It was isolated at the University of Toronto in 1921 and first given to a patient, Leonard Thompson, in January 1922, which makes it the first peptide put to therapeutic use and the drug that opened the whole field. For decades it was extracted from animal pancreas; since 1982 it has been made by genetically engineered microorganisms.

When was insulin discovered?

Insulin was isolated at the University of Toronto in 1921 by Frederick Banting and Charles Best, working in J. J. R. Macleod’s laboratory with the biochemist James Collip. The first patient was treated in January 1922, and Banting and Macleod shared the 1923 Nobel Prize in Physiology or Medicine for the discovery.

What was the first genetically engineered drug?

Recombinant human insulin, sold as Humulin. It was developed using technology from Genentech, licensed to Eli Lilly, and approved by the US Food and Drug Administration in 1982, which made it the first recombinant DNA product approved for medical use. Instead of being extracted from animal pancreas, it was produced by engineered bacteria carrying a synthetic human insulin gene.

Who invented solid-phase peptide synthesis?

Robert Bruce Merrifield, who published the method in 1963 while at the Rockefeller Institute. Solid-phase peptide synthesis builds a peptide one protected amino acid at a time on an insoluble resin bead, which made peptide synthesis fast, reproducible and eventually automatable. Merrifield received the 1984 Nobel Prize in Chemistry for the work.

When was the first GLP-1 drug approved?

The first GLP-1 receptor agonist, exenatide (Byetta), was approved by the FDA on 28 April 2005 for type 2 diabetes. Its sequence was based on exendin-4, a peptide found in the venom of the Gila monster. Later GLP-1 medicines include liraglutide (2010) and semaglutide (2017), and the dual GIP/GLP-1 agonist tirzepatide followed in 2022.

How many peptide drugs have been approved?

Published reviews put the number of therapeutic peptides on the market at roughly 80 worldwide, with a few hundred more in clinical development. The figure depends on where the line between a peptide and a small protein is drawn, and it rises every year, so any single count is a snapshot rather than a fixed total.

Is a research peptide the same as an approved peptide drug?

No. An approved peptide drug has been through regulatory review and is manufactured under an inspected quality system for use in medicine. A research-grade peptide that shares the same name and sequence is made to a supplier’s own specification for laboratory use, has not been through that review, and is not the approved medicine. Sharing a name is not the same as being the same product.

What is the newest peptide drug?

The most recent wave of approvals has been in the GLP-1 class. Tirzepatide, a dual GIP/GLP-1 receptor agonist, was approved as Mounjaro in 2022 and as Zepbound in 2023, and triple-receptor agonists such as retatrutide have been studied in clinical trials. Because approvals happen continually, the newest entry changes from year to year.

References

1. UMass Chan Medical School, Diabetes Center of Excellence. Leonard Thompson Received the First Human Insulin Injection to Treat Diabetes (January 1922). https://www.umassmed.edu/dcoe/diabetes-education/patient-resources/first-insulin-injection/
2. Thomas Fisher Rare Book Library, University of Toronto. Leonard Thompson — The Discovery of Insulin at the University of Toronto. https://fisherdigitus.library.utoronto.ca/exhibits/show/insulin100/early-patients/leonard-thompson
3. The Nobel Prize in Physiology or Medicine 1923 — Frederick Grant Banting and John James Rickard Macleod, “for the discovery of insulin.” NobelPrize.org. https://www.nobelprize.org/prizes/medicine/1923/summary/
4. The Nobel Prize in Chemistry 1958 — Frederick Sanger, for work on the structure of proteins, especially insulin. NobelPrize.org. https://www.nobelprize.org/prizes/chemistry/1958/sanger/facts/
5. The Nobel Prize in Chemistry 1955 — Vincent du Vigneaud, for the first synthesis of a polypeptide hormone. NobelPrize.org. https://www.nobelprize.org/prizes/chemistry/1955/vigneaud/facts/
6. Merrifield, R. B. (1963). Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide. Journal of the American Chemical Society, 85(14), 2149–2154. doi:10.1021/ja00897a025
7. The Rockefeller University. R. Bruce Merrifield — 1984 Nobel Prize in Chemistry. https://www.rockefeller.edu/our-scientists/r-bruce-merrifield/2398-nobel-prize/
8. Goeddel, D. V., Kleid, D. G., Bolivar, F., Heyneker, H. L., et al. (1979). Expression in Escherichia coli of chemically synthesized genes for human insulin. Proceedings of the National Academy of Sciences USA, 76(1), 106–110. doi:10.1073/pnas.76.1.106
9. Smithsonian National Museum of American History. Recombinant Drugs (Birth of Biotech collection). https://americanhistory.si.edu/collections/object-groups/birth-of-biotech/recombinant-drugs
10. American Council on Science and Health (28 October 2019). Record-Time FDA Approval of Human Insulin in 1982: When Genetic Engineering Came of Age. https://www.acsh.org/news/2019/10/28/record-time-fda-approval-human-insulin-1982-when-genetic-engineering-came-age-14362
11. Clinical development of the GnRH agonist leuprolide acetate depot. F&S Reports (2022). https://www.fertstertreports.org/article/S2666-3341(22)00122-2/fulltext
12. Octreotide (somatostatin analogue): approval history and overview. https://en.wikipedia.org/wiki/Octreotide
13. FUZEON (enfuvirtide) for Injection — FDA prescribing information (2003). U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021481lbl.pdf
14. Ziconotide (Prialt), a synthetic cone-snail venom peptide: history and overview. https://en.wikipedia.org/wiki/Ziconotide
15. Eng, J., Kleinman, W. A., Singh, L., Singh, G., & Raufman, J. P. (1992). Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Journal of Biological Chemistry.
16. Byetta (exenatide) FDA Approval History. Drugs.com. https://www.drugs.com/history/byetta.html
17. Victoza (liraglutide) FDA Approval History. Drugs.com. https://www.drugs.com/history/victoza.html
18. Saxenda (liraglutide) FDA Approval History. Drugs.com. https://www.drugs.com/history/saxenda.html
19. Ozempic (semaglutide) FDA Approval History. Drugs.com. https://www.drugs.com/history/ozempic.html
20. Rybelsus (semaglutide) FDA Approval History. Drugs.com. https://www.drugs.com/history/rybelsus.html
21. Wegovy (semaglutide) FDA Approval History. Drugs.com. https://www.drugs.com/history/wegovy.html
22. Eli Lilly and Company (13 May 2022). FDA Approves Lilly’s Mounjaro (tirzepatide) Injection, the First and Only GIP and GLP-1 Receptor Agonist for the Treatment of Adults with Type 2 Diabetes. https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-mounjarotm-tirzepatide-injection-first-and
23. Zepbound (tirzepatide) FDA Approval History. Drugs.com. https://www.drugs.com/history/zepbound.html
24. GLP-1 poly-agonist peptides (including triple-receptor agonists such as retatrutide): overview. https://en.wikipedia.org/wiki/GLP1_poly-agonist_peptides
25. Muttenthaler, M., King, G. F., Adams, D. J., & Alewood, P. F. (2021). Trends in peptide drug discovery. Nature Reviews Drug Discovery, 20(4), 309–325. doi:10.1038/s41573-020-00135-8
26. Big peptide drugs in a small molecule world. Frontiers in Chemistry (2023), 11, 1302169. doi:10.3389/fchem.2023.1302169

For more on the themes this history touches, see How Peptides Are Made for the manufacturing chemistry, Where Are Peptides Made? for where the industry sits today, Recombinant vs Synthetic Peptides for the two production routes, Peptide vs Drug vs Biologic for the regulatory categories, and What Are Peptides? for the basics.

All Patriot Labs products are sold strictly for in-vitro research and laboratory use only. Not for human or veterinary consumption. This guide is educational and describes the history of peptide science and industry in general terms; it is not medical advice, does not describe how to use any product, and makes no claim about the properties or effects of any specific product.