One gene, four human peptides
GLP-1 is not made on its own. The human gene called GCG produces a precursor, proglucagon, which is cut into four mature peptides [1]. Glucagon comes from the pancreas and raises blood sugar between meals. GLP-1 and GLP-2 are released by L-cells in the gut after eating. The NCBI gene summary describes GLP-1 as boosting insulin release when glucose is high, curbing glucagon, slowing stomach emptying and promoting fullness, and GLP-2 as acting mainly on the gut, supporting its lining and nutrient absorption. The fourth peptide resembles glicentin, another gut hormone [1].
That is the whole family in humans. There is a GLP-1 and a GLP-2, and no GLP-3 [1]. The US labels for semaglutide and tirzepatide describe GLP-1 as a physiological regulator of appetite and calorie intake, which is the effect the weight medicines build on [3][4].
GLP-2: the sibling with a different job
GLP-2 has its own receptor and its own medicine. Teduglutide is a 33-amino-acid analogue of human GLP-2 approved in the United States for adults and children aged 1 and older with short bowel syndrome who depend on intravenous nutrition or fluids [2]. Its label says GLP-2 increases blood flow to the intestine and reduces stomach acid, and that teduglutide improves absorption in the gut [2]. It is not a weight-loss medicine, which shows that the “GLP” numbers name different hormones, not stronger versions of the same one.
Where a real GLP-3 exists
A peptide called glucagon-like peptide 3 has been described in biology, just not in people. A genetic survey of 28 fish species found that the proglucagon gene of cartilaginous fish, the group that includes sharks and rays, encodes a novel GLP-3 alongside glucagon, GLP-1 and GLP-2 [5]. A 2024 laboratory study in the Pacific spiny dogfish, a small shark, found that this GLP-3 changed ketone handling in the liver [6]. Neither study concerns human medicine.
What people usually mean by “GLP-3”
In everyday use the term has drifted to mean a medicine that acts on three hormone receptors. Tirzepatide already acts on two: the GIP receptor and the GLP-1 receptor [4]. Retatrutide, developed by Eli Lilly, is described in its trials as a triple agonist of the GIP, GLP-1 and glucagon receptors [7][8][9]. A 2025 nutrition advisory from four obesity and nutrition societies refers to this group as dual and triple receptor agonists, not as GLP-3 [11].
None of the official documents we checked for this article uses “GLP-3”: not the US prescribing information, the European product information or the FDA pages. The accurate words are “triple agonist” or the drug’s own name.
What the retatrutide trials have reported
All three trials were funded by the manufacturer. In TRIUMPH-2, stopping treatment because of side effects or death was more frequent at the 9 mg and 12 mg doses than on placebo [9]. These are trial results in carefully monitored participants; they do not amount to an approval, and the doses studied are not a guide for anyone.
| Trial | Who took part | Mean weight change, retatrutide vs placebo | Safety notes in the abstract |
|---|---|---|---|
| Phase 2, 48 weeks [8] | 338 adults with obesity or overweight with a weight-related condition | −8.7% to −24.2% across doses vs −2.1% | Mostly gastrointestinal, dose-related, often mild to moderate; heart rate rose, peaking at 24 weeks |
| TRIUMPH-1, phase 3, 80 weeks [7] | 2,339 adults with obesity, without diabetes | −17.6%, −23.7% and −25.0% (4, 9, 12 mg) vs −3.9% | Most common adverse events gastrointestinal |
| TRIUMPH-2, phase 3, 80 weeks [9] | 1,152 adults with obesity and type 2 diabetes | −11.9%, −16.8% and −18.8% vs −5.1% | Diarrhea and nausea more common; low blood pressure and dysesthesia (abnormal skin sensations) more frequent than on placebo |
Is retatrutide approved?
Not as of the FDA’s page current on 1 October 2026. The FDA says retatrutide and cagrilintide are not components of any FDA-approved drug, have not been found safe and effective for any condition, and cannot be used in compounding under federal law [10]. It has warned telehealth companies over marketing retatrutide, ingredient distributors over selling it to compounders, and companies selling it labelled “for research purposes” or “not for human consumption” [10].
Products sold online under those labels are of unknown quality, the FDA says, and it urges consumers not to buy them [10]. A separate article on PepLabo covers what “research use only” means for peptides.
Wegovy® is a registered trademark of Novo Nordisk A/S and Zepbound® a registered trademark of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Novo Nordisk, Eli Lilly and Company or any other manufacturer mentioned.
When to get help
| Sign | Who to contact | How fast | Source |
|---|---|---|---|
| Severe stomach pain, a severe allergic reaction or fainting after using any injectable product bought online | Emergency services (112/911) | Emergency | FDA [10]; Wegovy® Medication Guide [3] |
| You have been offered retatrutide or another unapproved GLP-1 as a “research” product | Do not use it; talk to your prescriber about approved options | At your next appointment | FDA [10] |
