Semaglutide and tirzepatide can seem to have come out of nowhere, but the first GLP-1 medication was approved in 2005, and its story starts with the saliva of a desert lizard. This guide walks through every GLP-1 drug approved in the U.S., who made it, which ones are still sold, how they compare, and what's still in development.
Longer than you might think
Most people heard about GLP-1 medications in the last few years, through semaglutide and tirzepatide. The drug class itself is two decades old, and the science behind it is older still.
Where it started
The GLP-1 hormone was identified in the 1980s, during research into gut hormones that regulate insulin. The step that made a drug possible came from an odd place: exendin-4, a peptide in the saliva of the Gila monster, a venomous lizard. Exendin-4 activates the same receptor as human GLP-1 but isn't broken down as quickly, which is what limits natural GLP-1 as a drug. It became the basis for the first approved GLP-1 medication.
The full approval timeline
| Year (approx.) | Medication | Generic name | Manufacturer | Notes |
|---|---|---|---|---|
| 2005 | Byetta | Exenatide | Amylin Pharmaceuticals (later Eli Lilly / AstraZeneca) | First GLP-1 receptor agonist approved; twice-daily injection; derived from exendin-4. AstraZeneca stopped selling it in the U.S. in October 2024; an FDA-approved generic exenatide exists |
| 2010 | Victoza | Liraglutide | Novo Nordisk | Once-daily injection for type 2 diabetes |
| 2012 | Bydureon (2012; Bydureon BCise 2017) | Exenatide (extended-release) | Amylin / AstraZeneca | Once-weekly version of exenatide. The original Bydureon was withdrawn from sale in 2021, and AstraZeneca discontinued Bydureon BCise in the U.S. in October 2024 |
| 2014 | Tanzeum | Albiglutide | GSK | Once-weekly; discontinued by the manufacturer in 2017-2018 for commercial reasons, not safety |
| 2014 | Trulicity | Dulaglutide | Eli Lilly | Once-weekly injection for type 2 diabetes |
| 2014 | Saxenda | Liraglutide (weight-management dose) | Novo Nordisk | First GLP-1 approved specifically for chronic weight management |
| 2016 | Adlyxin | Lixisenatide | Sanofi | Once-daily; approved earlier in Europe as Lyxumia (2013). Discontinued in the U.S. by 2023; the FDA's Purple Book lists it as discontinued |
| 2017 | Ozempic | Semaglutide | Novo Nordisk | Once-weekly injection for type 2 diabetes |
| 2019 | Rybelsus | Semaglutide (oral) | Novo Nordisk | First oral GLP-1 medication; a reformulated version went on sale in the US as Ozempic tablets on May 4, 2026 (4 mg and 9 mg correspond to Rybelsus 7 mg and 14 mg; not interchangeable mg-for-mg) |
| 2021 | Wegovy | Semaglutide (weight-management dose) | Novo Nordisk | Approved specifically for chronic weight management |
| 2022 | Mounjaro | Tirzepatide | Eli Lilly | First dual GIP/GLP-1 agonist; approved for type 2 diabetes |
| 2023 | Zepbound | Tirzepatide (weight-management dose) | Eli Lilly | Dual agonist approved for chronic weight management |
| 2025 | Wegovy pill | Semaglutide (oral, 25 mg) | Novo Nordisk | First oral GLP-1 approved for weight management; once-daily tablet (FDA approval December 22, 2025, per Novo Nordisk (external link)) |
| 2026 | Foundayo | Orforglipron | Eli Lilly | First oral, non-peptide GLP-1 medication approved for weight management (FDA approval April 1, 2026) |
Approval years are U.S. FDA approvals and are approximate for older medications. The field moves quickly, so confirm current status with the FDA or the manufacturer. Approval and marketing statuses in this table and the pipeline section were last verified in September 2026.
How to think about the comparison
A few patterns help more than memorizing the table.
Dosing has become less frequent over time. Exenatide was twice daily, liraglutide once daily, and dulaglutide, semaglutide and tirzepatide once weekly. Now there are once-daily pills (Rybelsus, the Wegovy pill and Foundayo) that need no injection at all.
The same active ingredient is often sold under two brand names, one for diabetes and one for weight management. Ozempic and Wegovy (semaglutide) are the clearest case of the weight-management brand going higher: 2 mg for Ozempic vs 2.4 mg for Wegovy, and as of September 2026 the Wegovy label allows up to 7.2 mg for some adults. Mounjaro and Zepbound (tirzepatide) share an identical ladder, so the difference there is the label and coverage, not the dose. Our guide on understanding insurance coverage explains why that matters.
Later drugs have generally shown larger average weight loss in trials. Semaglutide, a single-pathway GLP-1 drug, generally beat earlier ones like liraglutide and exenatide, and tirzepatide, a dual GIP/GLP-1 agonist, has generally beaten single-pathway GLP-1 drugs.
Approval doesn't guarantee a drug stays on the market. Several approved GLP-1 drugs are no longer sold in the U.S.: albiglutide (Tanzeum) since 2018, lixisenatide (Adlyxin) by 2023, and the branded exenatide products Byetta and Bydureon BCise since 2024. In each case the manufacturer cited business reasons, not safety. That's 4 of the 14 products in the table.
For the trials behind each drug (what it tested, who funded it, and what it found), see our guide to the key GLP-1 clinical trials.
What's still in the pipeline (not yet approved)
As of September 2026 none of these is FDA-approved, and timelines can slip, so check current status before relying on them:
- CagriSema (Novo Nordisk) combines semaglutide with cagrilintide, an amylin analog, to act on two appetite-regulating hormone pathways. Novo Nordisk submitted it to the FDA in December 2025, and a decision is expected in 2026.
- Retatrutide (Eli Lilly) is a "triple agonist" that activates GLP-1, GIP and glucagon receptors together. Early trial data showed substantial weight loss.
- Survodutide (Boehringer Ingelheim / Zealand Pharma) is a dual GLP-1/glucagon receptor agonist in late-stage trials.
- Amycretin (Novo Nordisk) is a combined GLP-1/amylin receptor agonist being tested as both an injection and a pill.
Trials are also still adding to what we know about approved drugs. SURMOUNT-MAINTAIN (2026) tested how well weight loss holds on tirzepatide at full vs reduced dose, compared with stopping. At week 112, people who stayed on their maximum tolerated dose were down 21.9% from baseline, those reduced to 5 mg were down 16.6%, and those switched to placebo were down 9.9%. Rescue treatment for regain was needed by 8%, 25% and 67% respectively (Horn et al., The Lancet, 2026, DOI (external link)). Those numbers bear on long-term treatment and on weight regain after a dose reduction; our guide to tapering vs. staying on a maintenance dose covers what the trial means in practice.
Study findings above are attributed to their authors and were located via PubMed.
This article is for general education and is not medical advice. Talk with your prescriber or care team about your own situation.