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History of GLP-1 drugs: from a fish gene to weekly shots

Updated Sep 30, 2026. Numbers in brackets link to the source each fact comes from.

GLP-1 drugs grew out of decades of basic research on the hormones that control blood sugar. A gene found in anglerfish in the early 1980s pointed to the hormone GLP-1 [1], a peptide in Gila monster venom showed how to make it last, and the FDA approved the first drug in the class in 2005 [9].

A hormone hiding next to glucagon

Scientists had suspected for a long time that the gut tells the pancreas to release insulin after a meal. Solid evidence came in 1964, when researchers showed that glucose swallowed triggers more insulin than glucose injected into a vein [3]. The gut signal behind it, called an incretin, was still unknown.

The clue came from fish. In 1982, researchers funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) found the anglerfish glucagon gene and, next to it, a gene for a protein similar to glucagon but different, which they named “glucagon-like peptide” [1]. Joel Habener reported the same year that the gene’s product contains a second glucagon-like peptide [2].

Svetlana Mojsov and Habener then showed that a shorter form of GLP-1 exists in the intestine, published in 1986 [4]. In 1987 they showed that tiny amounts of that form trigger insulin release from rat pancreases [5]. GLP-1 was the missing incretin.

The problem: GLP-1 disappears in minutes

Natural GLP-1 breaks down within minutes of entering the blood [8]. That made it useless as a medicine on its own.

The first fix came from the desert. NIDDK scientists studying the Gila monster found proteins in its venom-laced saliva that seemed to restart its digestion after months without food [6]. One of them, exendin-4, is close to GLP-1 but survives in the blood for about 12 hours instead of a few minutes [7]. A synthetic copy, exenatide, was approved by the FDA as Byetta in April 2005 [9]. Drugs@FDA now lists the original Byetta products as discontinued [10].

Making GLP-1 last a day, then a week

At Novo Nordisk, Lotte Bjerre Knudsen’s team took another route: attaching fatty acids to GLP-1 so it stays in the body longer [11]. The result was liraglutide, which lasts 24 hours, and later semaglutide, which lasts a week [12]. Liraglutide was approved in Europe for type 2 diabetes in 2009, with the FDA following a year later [13], in January 2010 as Victoza [14].

Trials of these diabetes drugs kept showing the same side effect: people lost weight [15]. That opened a second use. In December 2014 the FDA approved liraglutide as Saxenda, the first GLP-1 drug approved to treat obesity [16] [17].

Approval timeline in the US

These are the original FDA approval dates from Drugs@FDA, the agency’s approval database [9]:

Approved Drug What it was
April 2005 Byetta (exenatide) First GLP-1 drug, for type 2 diabetes [9]
January 2010 Victoza (liraglutide) Once-daily shot for type 2 diabetes [14]
December 2014 Saxenda (liraglutide) First GLP-1 approved for obesity [17]
December 2017 Ozempic (semaglutide) Weekly shot for type 2 diabetes [18]
September 2019 Rybelsus (semaglutide) A tablet form for type 2 diabetes [19]
June 2021 Wegovy (semaglutide) Weekly shot for weight management [20]
May 2022 Mounjaro (tirzepatide) Weekly shot for type 2 diabetes [21]
November 2023 Zepbound (tirzepatide) Weekly shot for weight management [22]
December 2024 Zepbound Added use for sleep apnea [24]
December 2025 Wegovy tablets A daily pill form of Wegovy [27]
March 2026 Wegovy HD A new higher-dose regimen [28]
April 2026 Foundayo (orforglipron) A daily pill for weight management [29]

Tirzepatide works a little differently: its label describes it as acting on both the GIP and GLP-1 receptors [23]. For current approved uses of each drug, see what each GLP-1 is approved for.

The Lasker Award

In 2024 the Lasker Foundation gave its clinical research award for the discovery and development of GLP-1 drugs for obesity [25]. It named Habener and Mojsov for identifying the active form of the hormone, and Knudsen for turning it into weight-loss medicines [26]. The award did not name the Gila monster researchers, whose work on exendin-4 NIDDK credits in its own history [6].

What comes next

You may see newer compound names online. The FDA says retatrutide and cagrilintide are not part of any FDA-approved drug and have not been found safe and effective for any condition, and that they cannot legally be used in compounding [30]. Anything sold as one of them today is unapproved. See fake and unapproved GLP-1 products.

Sources

  1. In fact, the next clue to the incretin mystery was uncovered during the 1982 discovery of the anglerfish glucagon gene: an adjacent gene turned out to encode a protein that is notably similar to glucagon, yet clearly different from it. The researchers therefore called it a “glucagon-like peptide,” or GLP. niddk.nih.gov, read Sep 27, 2026.
  2. In 1982, Habener reported that the fish glucagon gene encodes a predicted precursor protein that contains glucagon and, in addition, a second peptide that resembles glucagon. laskerfoundation.org, read Sep 27, 2026.
  3. Solid evidence for such “incretins” emerged in 1964, when researchers demonstrated that ingested glucose elicits more insulin release than injected glucose does. laskerfoundation.org, read Sep 27, 2026.
  4. This smaller peptide thus exists in nature and, notably, in the intestine, Mojsov, Habener, and their collaborators reported in 1986. laskerfoundation.org, read Sep 27, 2026.
  5. Mojsov and Habener teamed up with Gordon Weir (Joslin Diabetes Center) and, in 1987, demonstrated that tiny concentrations of pure GLP-1 (7-37), such as those in the bloodstream, stimulate insulin secretion from isolated rat pancreases that continue to function even when removed from the body. laskerfoundation.org, read Sep 27, 2026.
  6. At about the same time that the glucagon-like peptides were being discovered by NIDDK grantees, NIDDK intramural scientists working with the lizard, called a “Gila monster,” discovered that mingling with the venom in the lizard’s saliva were proteins that appeared to “jump- start” its digestive system after the months of fasting that normally occur between its meals. niddk.nih.gov, read Sep 27, 2026.
  7. Importantly, a small but significant difference between the GLP-1 and exendin-4 structures protects the latter from digestion in the blood, where GLP-1 disappears within a few minutes, yet exendin-4 persists for about 12 hours. niddk.nih.gov, read Sep 27, 2026.
  8. In the human body, GLP-1 vanishes minutes after it enters the bloodstream. laskerfoundation.org, read Sep 27, 2026.
  9. 04/28/2005 ORIG-1 Approval Type 1 - New Molecular Entity accessdata.fda.gov, read Sep 27, 2026.
  10. BYETTA EXENATIDE SYNTHETIC 300MCG/1.2ML (250MCG/ML) INJECTABLE;SUBCUTANEOUS Discontinued accessdata.fda.gov, read Sep 27, 2026.
  11. After toying with a slow-release formulation and ones that resisted DPP-4-mediated destruction, she settled on a strategy of attaching fatty acids to GLP-1. laskerfoundation.org, read Sep 27, 2026.
  12. Subsequent FDA approvals went to even longer-lived forms of GLP-1, like liraglutide, which lasts 24 hours, and semaglutide, which lasts an entire week. niddk.nih.gov, read Sep 27, 2026.
  13. The European Medicines Agency (EMA) approved liraglutide (Victoza®) to control blood sugar levels in type 2 diabetes in 2009, and the U.S. Food and Drug Administration (FDA) followed the next year. laskerfoundation.org, read Sep 27, 2026.
  14. 01/25/2010 ORIG-1 Approval Type 1 - New Molecular Entity accessdata.fda.gov, read Sep 27, 2026.
  15. Another exciting finding from randomized clinical trials of these therapeutics is that people taking these medications typically lose a significant amount of weight. niddk.nih.gov, read Sep 27, 2026.
  16. The FDA and EMA gave it the green light in 2014 and 2015, respectively, and it was the first GLP-1-based drug approved for the treatment of obesity (Saxenda®). laskerfoundation.org, read Sep 27, 2026.
  17. 12/23/2014 ORIG-1 Approval STANDARD accessdata.fda.gov, read Sep 27, 2026.
  18. 12/05/2017 ORIG-1 Approval Type 1 - New Molecular Entity accessdata.fda.gov, read Sep 27, 2026.
  19. 09/20/2019 ORIG-1 Approval Type 3 - New Dosage Form accessdata.fda.gov, read Sep 27, 2026.
  20. 06/04/2021 ORIG-1 Approval PRIORITY accessdata.fda.gov, read Sep 27, 2026.
  21. 05/13/2022 ORIG-1 Approval Type 1 - New Molecular Entity accessdata.fda.gov, read Sep 27, 2026.
  22. 11/08/2023 ORIG-1 Approval PRIORITY accessdata.fda.gov, read Sep 27, 2026.
  23. Tirzepatide is a GIP receptor and GLP-1 receptor agonist. dailymed.nlm.nih.gov, read Sep 27, 2026.
  24. 12/20/2024 SUPPL-13 Efficacy-New Indication accessdata.fda.gov, read Sep 27, 2026.
  25. The 2024 Lasker~DeBakey Clinical Medical Research Award honors three scientists for their discovery and development of GLP-1-based drugs that have revolutionized the treatment of obesity. laskerfoundation.org, read Sep 27, 2026.
  26. Joel Habener (Massachusetts General Hospital) and Svetlana Mojsov (The Rockefeller University) discerned the physiologically active form of the hormone, and Lotte Bjerre Knudsen (Novo Nordisk) turned it into medications that promote weight loss. laskerfoundation.org, read Sep 27, 2026.
  27. 12/22/2025 ORIG-1 Approval Type 3 - New Dosage Form accessdata.fda.gov, read Sep 27, 2026.
  28. 03/19/2026 SUPPL-29 Efficacy-New Dosing Regimen accessdata.fda.gov, read Sep 27, 2026.
  29. 04/01/2026 ORIG-1 Approval Type 1 - New Molecular Entity accessdata.fda.gov, read Sep 27, 2026.
  30. Retatrutide and cagrilintide cannot be used in compounding under federal law. Additionally, these are not components of FDA-approved drugs and have not been found safe and effective for any condition. fda.gov, read Sep 27, 2026.