Before any medicine: how GLP-1 was found
The idea behind these medicines is more than a century old. A large peer-reviewed review traces it to the early 1900s: secretin, the first gut hormone, was described in 1902, and in 1929 a fraction of gut extract that lowered blood sugar in animals was given the name “incretin” [2]. Once insulin could be measured in blood in the 1960s, researchers found that sugar taken by mouth releases much more insulin than sugar given into a vein, which became known as the incretin effect [2].
GIP was the first incretin to be identified, between 1969 and 1971 [2]. GLP-1 came out of gene work. In the early 1980s, reading the proglucagon gene, first in anglerfish and then in mammals including humans, revealed two peptides resembling glucagon, which were named GLP-1 and GLP-2 [2]. A shortened form of GLP-1 extracted from human and pig gut was then shown to boost insulin release, in laboratory models and later in people [2]. Descriptions of GLP-1 binding to receptors in the brain and pancreas were published in 1987 and 1988 [3].
Natural GLP-1 had one serious drawback as a drug: it survives only a minute or two in the bloodstream, because the enzyme DPP-4 cuts it and the kidneys clear it [2]. Each medicine in this history is, in its own way, a solution to that problem.
Reading the “Initial U.S. Approval” line
Every US prescribing information shows a year under the product name. The FDA explains that it marks the year a new molecular entity was first approved, not the year a particular brand appeared; its own example is a statin labelled 1996 because that is when the molecule was first approved [1].
That is why the Ozempic®, Wegovy® and Rybelsus® labels all say 2017, the year of semaglutide, and Victoza® and Saxenda® say 2010 for liraglutide. Zepbound® shows the rule clearly: its label says 2022, the year tirzepatide was first approved as Mounjaro®, although Zepbound® itself was approved in November 2023 [9][26].
Each molecule’s first US approval
The table lists the original approval date recorded in Drugs@FDA for each GLP-1 molecule, with the brands named in this article and their own approval dates [6]. It includes two molecules the earlier version of this article left out, albiglutide and lixisenatide.
| First approved | Molecule | Brands and their approval dates | Form |
|---|---|---|---|
| 28 April 2005 | exenatide | Byetta® (2005); Bydureon® (January 2012); Bydureon BCise® (October 2017) | twice-daily injection; weekly extended-release injection |
| 25 January 2010 | liraglutide | Victoza® (2010); Saxenda® (December 2014) | once-daily injection |
| 15 April 2014 | albiglutide | Tanzeum® (2014; now listed as discontinued) | injection |
| 18 September 2014 | dulaglutide | Trulicity® (2014) | once-weekly injection |
| 27 July 2016 | lixisenatide | Adlyxin® (2016) | once-daily injection |
| 5 December 2017 | semaglutide | Ozempic® (2017); Rybelsus® (September 2019); Wegovy® (June 2021); Wegovy® tablets (December 2025); Ozempic® tablets (name approved January 2026) | once-weekly injection; once-daily tablets |
| 13 May 2022 | tirzepatide | Mounjaro® (2022); Zepbound® (November 2023) | once-weekly injection |
| 1 April 2026 | orforglipron | Foundayo™ (2026) | once-daily tablet |
2005 to 2017: making the effect last longer
Exenatide is a synthetic copy of exendin-4. A 1992 laboratory study isolated this 39-amino-acid peptide from the venom of the Gila monster, Heloderma suspectum [4], and the Byetta® label still describes exenatide as first identified in that lizard [5]. The GLP-1 review explains that exendin-4 differs from human GLP-1 at the second amino acid, which protects it from DPP-4 [2]. Even so, the Byetta® label gives a mean half-life of 2.4 hours, which is why that product was injected twice a day [5]. Bydureon® kept the same molecule but released it slowly from a depot of microspheres under the skin, allowing a weekly injection [2].
Liraglutide took another route. Its developers attached a fatty acid to a human GLP-1 analogue so that it binds reversibly to albumin, one of the most abundant and stable proteins in plasma, and stays in circulation longer [3]. Their review notes that liraglutide was authorised in the EU in 2009, four years after exenatide’s US approval [3]; the FDA approved it as Victoza® for type 2 diabetes in January 2010 and as Saxenda® for weight management in December 2014 [6].
Dulaglutide (Trulicity®) was approved in 2014 as a weekly injection, and two further molecules, albiglutide (Tanzeum®) and lixisenatide (Adlyxin®), were approved in 2014 and 2016 [6]. Semaglutide, approved as Ozempic® in December 2017, used a refined version of the albumin approach [3][6]. The Wegovy® label gives it 94% sequence homology with human GLP-1 and a half-life of about one week [25].
2019 to 2023: tablets, obesity and a second hormone
In September 2019 the FDA approved Rybelsus®, semaglutide as a daily tablet for blood sugar control in type 2 diabetes [6]. The tablets contain an absorption enhancer called SNAC, which the labels say helps semaglutide get absorbed; even so, the Wegovy® label estimates that only 1% to 2% of a tablet dose reaches the bloodstream, against 89% for the injection [25].
In June 2021 semaglutide was approved for a third time, as Wegovy®, for weight in adults with a BMI of 30 or more, or 27 or more with at least one weight-related condition [19]. A December 2022 supplement extended Wegovy® to adolescents aged 12 and older with obesity [6].
Tirzepatide then added a second target. Mounjaro® was approved on 13 May 2022 to improve blood sugar control in diabetes [7], and its sister label describes tirzepatide as a GIP receptor and GLP-1 receptor agonist [26]. The same molecule was approved as Zepbound® for weight on 8 November 2023 [9].
New uses, 2020 to 2026
Since 2020 most milestones have been new indications for molecules that already existed. Each rests on its own outcome trial and changes what the label says the medicine is for. The table shows a selection, each from an FDA letter or announcement.
| Date | Medicine | What was added | Source |
|---|---|---|---|
| 16 January 2020 | Ozempic® | Lower risk of major cardiovascular events in type 2 diabetes with established heart disease | Drugs@FDA letter [6] |
| 8 March 2024 | Wegovy® | Lower risk of cardiovascular death, heart attack and stroke in adults with heart disease and obesity or overweight | FDA press release [10] |
| 20 December 2024 | Zepbound® | Obstructive sleep apnea of moderate or severe degree in adults who have obesity; the FDA called it the first drug treatment for these patients | FDA press release [11] |
| 28 January 2025 | Ozempic® | Lower risk of sustained eGFR decline, end-stage kidney disease and cardiovascular death in type 2 diabetes with chronic kidney disease | FDA letter [13] |
| 15 August 2025 | Wegovy® | MASH, a serious fatty liver disease, with moderate to advanced fibrosis, under accelerated approval | FDA announcement [12] |
| 17 October 2025 | Rybelsus® | Lower risk of major cardiovascular events in high-risk type 2 diabetes; the type 1 diabetes limitation of use removed | FDA letter [14] |
| 19 December 2025 | Mounjaro® | Children aged 10 and older with type 2 diabetes | FDA letter [15] |
| 22 December 2025 | Wegovy® tablets | A tablet product for weight reduction and for lowering cardiovascular risk | FDA letter [16] |
| 27 August 2026 | Mounjaro® | Lower risk of major cardiovascular events in high-risk type 2 diabetes, based on a trial against dulaglutide | FDA letter [17] |
Shortages, compounding and the first generics
Demand grew faster than supply. FDA records show semaglutide and tirzepatide injections in shortage from 2022 [20]. The agency declared the tirzepatide shortage over on 19 December 2024, after re-evaluating an October decision, and the semaglutide shortage over on 21 February 2025 [20]. Shortage status matters for compounding, because once a shortage is resolved the FDA generally treats the drug as commercially available [20]. On 30 April 2026 the FDA proposed keeping semaglutide, tirzepatide and liraglutide off the list of bulk substances that outsourcing facilities may use, saying it found no clinical need [21]. The article on compounded GLP-1s covers those rules.
Liraglutide is the exception. On 20 October 2026 the FDA shortage database still showed liraglutide injection as currently in shortage, an entry first posted on 18 July 2023 [22].
The same years brought the first generic GLP-1 medicines: exenatide referencing Byetta® on 19 November 2024, liraglutide referencing Victoza® on 23 December 2024 and liraglutide referencing Saxenda® on 27 August 2025 [23][24].
Brands that have left, or are leaving
A history also has exits. On 20 October 2026 Drugs@FDA listed every Byetta®, Bydureon® and Bydureon BCise® product as discontinued, and Tanzeum® as well [6]. A discontinued brand does not always mean the molecule is gone: a generic exenatide is approved [23].
Two further changes are under way, according to entries Novo Nordisk posted in the FDA shortage database. Manufacture of Rybelsus® 3, 7 and 14 mg tablets is being discontinued, with the entry stating that Ozempic® tablets will replace them, and Saxenda® is listed as available until its discontinuation in January 2027 [22]. The FDA had approved renaming the newer Rybelsus® tablet formulation as Ozempic® tablets on 30 January 2026 [18]. If you use one of these products, your pharmacist can tell you what remains available.
Labels change their words, and lose things
Each label’s “Recent Major Changes” box lists substantive changes to its main sections with the month and year [1]. Some changes are removals. The Wegovy® label lists its warning on suicidal behavior and ideation as removed in January 2026, and the Zepbound® and Saxenda® labels record the same removal in 2026 [25][26][27]. The October 2025 Rybelsus® approval also removed a limitation of use about type 1 diabetes [14].
Even the description of what a weight medicine is for has moved. Wegovy® in 2021 and Zepbound® in 2023 were approved for “chronic weight management” [19][9]; the current labels describe the purpose as reducing excess body weight and maintaining that reduction long term [25][26]. Information about a GLP-1 that is a few years old may describe a label that no longer exists, and the current revision is the one your prescriber and pharmacist work from.
What history does not tell you
An older molecule is not automatically better or worse than a newer one. Each label reports its own trials in its own population, against placebo or another medicine, and labels do not rank themselves. A long history does not mean every long-term question has been answered either: the MASH indication still depends on a trial that is running to 240 weeks [12].
The practical lesson is to check the molecule, the brand and the revision date of whatever you are reading. Which medicine, if any, suits you is a decision for your prescriber.
Ozempic®, Wegovy®, Rybelsus®, Saxenda® and Victoza® are registered trademarks of Novo Nordisk A/S. Mounjaro®, Zepbound® and Trulicity® are registered trademarks of Eli Lilly and Company; Foundayo™ is a trademark of Eli Lilly and Company. Byetta®, Bydureon® and Bydureon BCise® are trademarks of the AstraZeneca group of companies. Tanzeum® is a trademark of the GSK group of companies, and Adlyxin® is a trademark of Sanofi. PepLabo is not affiliated with or endorsed by Novo Nordisk, Eli Lilly and Company, AstraZeneca, GSK or Sanofi.