Substance classes · Classification
Anyone working with metabolic peptides runs into a numbering scheme sooner or later: GLP-1, GLP-2, GLP-3, and by now GLP-4 and GLP-5 as well. The sequence suggests a clear logic — each number a new, more potent generation. In reality it blends two entirely different things: genuine endogenous hormones and marketing labels from the grey market.
This page sets out what actually lies behind the designations, which substances are approved, which are in clinical testing and which have so far been examined only in animal studies. The subject here is strictly the development and approval status — not application, dosing or supply.
Why the numbering is misleading
GLP stands for glucagon-like peptide. There are exactly two endogenous hormones in this family: GLP-1 and GLP-2. Both arise from the same precursor molecule, proglucagon, and were described in the 1980s. The digits 1 and 2 are therefore biological designations for hormones that genuinely exist.
There is no GLP-3 in human physiology — and certainly no GLP-4 or GLP-5. These designations arose later, in the environment of online forums and supplier catalogues.
From “GLP-3” onwards, the number no longer counts hormones but the number of receptors a synthetic molecule acts on. A higher number therefore does not mean “more advanced” or “better” — merely “more receptors”, and with that a more complex, less readily surveyable profile of action.
On this way of counting, tirzepatide would be a “GLP-2” (two receptors: GLP-1 and GIP), retatrutide a “GLP-3” and so on. That produces an unfortunate double meaning: in the specialist literature “GLP-2” denotes an intestinal hormone, while in grey-market jargon it denotes a dual agonist for weight regulation. The two have nothing to do with one another.
For assessing a substance, the number is therefore worthless. Two other questions are decisive: how far has clinical development progressed? And do data in humans exist at all?
GLP-1 — the hormone everything grew out of
Approved
Preclinical › Phase 1 › Phase 2 › Phase 3 › Approval
GLP-1 is an incretin hormone released by the L-cells of the small intestine after food intake. It enhances glucose-dependent insulin secretion, inhibits glucagon release, slows gastric emptying and acts via receptors in the hypothalamus on satiety regulation. The natural hormone is broken down within a few minutes by the enzyme DPP-4 — the reason it is therapeutically unusable and stabilised analogues were developed.
These analogues are the best-studied substance class in the entire field. Approved GLP-1 receptor agonists include exenatide, liraglutide, dulaglutide and semaglutide. The last of these is approved in the European Union both for the treatment of type 2 diabetes (Ozempic) and for weight management in obesity (Wegovy). For these active substances, registration trials with several tens of thousands of participants and cardiovascular outcome trials running over several years are available.
GLP-2 — the second genuine hormone
Approved
Approved — but for a rare intestinal disease, not for weight regulation
GLP-2 arises from the same precursor as GLP-1 but has an entirely different task: it promotes the growth and regeneration of the intestinal mucosa, improves nutrient absorption and acts on intestinal blood flow. It has nothing to do with appetite regulation or weight loss.
The therapeutic analogue is called teduglutide and has been approved in the EU since 2012 under the name Revestive — as an orphan drug for the treatment of short bowel syndrome, a rare condition in which patients depend on parenteral nutrition after extensive intestinal resections. The approval was later extended to children.
When the grey market speaks of “GLP-2 peptides for weight loss”, the hormone GLP-2 is never what is meant; as a rule the reference is to tirzepatide — a synthetic dual agonist at the GLP-1 and GIP receptors. Tirzepatide is approved in the EU (Mounjaro), both for type 2 diabetes and for weight management. The designation “GLP-2” is simply incorrect for it.
“GLP-3” — retatrutide, the triple agonist
Phase 3
Preclinical › Phase 1 › Phase 2 › Phase 3 › Approval pending
Retatrutide is a synthetic, lipidated peptide that acts on three receptors simultaneously: GLP-1, GIP and glucagon. The glucagon receptor is the conceptual novelty here — its activation raises energy expenditure, while the two incretin components dampen food intake. The substance is being developed by Eli Lilly.
In May 2026 the results of the phase 3 trial TRIUMPH-1 were published: a randomised, double-blind, placebo-controlled study with 2,339 participants with obesity or overweight plus at least one weight-related comorbidity; people with diabetes were excluded. Three dose levels were examined over 80 weeks, with a blinded extension to 104 weeks for 532 participants with a baseline BMI of 35 kg/m² or above.
The highest dose level led to an average weight reduction of 28.3 percent (around 32 kg) after 80 weeks; after 104 weeks it was 30.3 percent (around 39 kg). In the middle dose group the reduction was 25.9 percent, in the lowest 19.0 percent. Of the highest-dose group, 45.3 percent achieved a weight reduction of at least 30 percent and 65.3 percent a BMI below 30 kg/m².
Adverse events were predominantly gastrointestinal and dose-dependent: in the highest-dose group, 42.4 percent reported nausea, 32.0 percent diarrhoea, 26.1 percent constipation and 25.3 percent vomiting. The discontinuation rate due to adverse events rose from 4.1 percent in the lowest to 11.3 percent in the highest dose group — a relevant finding, because it shows that the stronger effect is bought at the cost of poorer tolerability.
Placing the figures in context: they come from a controlled clinical trial with medical supervision, defined titration and accompanying care. They are not transferable to any other situation. Despite these data, retatrutide is not approved as a medicinal product in any country.
“GLP-4” — bioglutide (NA-931)
Phase 2
Preclinical › Phase 1 › Phase 2 › Phase 3 announced › Approval
Circulating under the designation “GLP-4” since 2025 is the substance NA-931, trade name Bioglutide, developed by Biomed Industries. It differs from the substances named so far in two respects.
First, the receptor profile is put together differently: alongside GLP-1, GIP and glucagon, NA-931 additionally addresses the IGF-1 receptor — not, as is often repeated, the amylin receptor. Second, the substance is orally available rather than injectable, which sets it structurally apart from the peptide injections in the development field.
At the EASD congress in Vienna in September 2025, phase 2 results were presented: a weight reduction of up to 13.8 percent at the highest dose examined, with 72 percent of those treated losing at least 12 percent of body weight, against 1.9 percent under placebo. Low gastrointestinal adverse events and no observed muscle loss were also reported.
Restraint is appropriate in assessing this. Phase 2 data come from considerably smaller cohorts than phase 3 trials, and the results have so far been communicated through a congress presentation and company announcements. Their evidential weight is therefore not comparable with the retatrutide data.
“GLP-5” — VRX-0075
Preclinical
Preclinical › Phase 1 › Phase 2 › Phase 3 › Approval — no data in humans
The currently highest number in the series denotes VRX-0075, a so-called quintuple agonist. The molecule activates five receptors: GLP-1, GIP and glucagon as with retatrutide, plus the amylin and calcitonin receptors. It was developed by researchers at the Indiana Biosciences Research Institute with research support from Eli Lilly.
The substance was presented as poster 2839-LB at the 86th Scientific Sessions of the American Diabetes Association on 7 June 2026 in New Orleans. It was reported that, at equimolar dosing in diet-induced obese rats, VRX-0075 produced a greater weight reduction than retatrutide, with a roughly 50 percent longer half-life than semaglutide and no notable findings in non-regulatory toxicology studies.
This is a purely preclinical substance. Only data from the animal model exist. No application for a clinical trial (IND) has been announced, no phase 1 study is registered, and there are no data whatsoever in humans. Enrolment of human participants would — if the programme is pursued further — realistically be possible at the earliest towards the end of the 2020s, with possible approval not before the middle of the following decade.
Overview: development status compared
| Designation | Substance | Receptors | Highest level of data | Approval |
|---|---|---|---|---|
| GLP-1 (hormone) | Semaglutide, liraglutide and others | GLP-1 | Phase 4 / long-term data | Yes (EU/USA), prescription-only |
| GLP-2 (hormone) | Teduglutide | GLP-2 | Registration trials | Yes, but for short bowel syndrome |
| “GLP-2” (jargon) | Tirzepatide | GLP-1, GIP | Phase 4 / long-term data | Yes (EU/USA), prescription-only |
| “GLP-3” | Retatrutide | GLP-1, GIP, glucagon | Phase 3 (TRIUMPH-1, 2026) | No |
| “GLP-4” | Bioglutide (NA-931) | GLP-1, GIP, glucagon, IGF-1 | Phase 2 (EASD 2025) | No |
| “GLP-5” | VRX-0075 | GLP-1, GIP, glucagon, amylin, calcitonin | Preclinical (rat, ADA 2026) | No |
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What the individual development stages mean
Preclinical means cell cultures and animal models. This status says nothing about efficacy and safety in humans. The great majority of all substances that reach this stage fail afterwards — effects in rodent models frequently cannot be transferred, and adverse effects only emerge in humans.
Phase 1 examines tolerability and pharmacokinetic behaviour in a small number of healthy volunteers. Phase 2 examines efficacy for the first time in a few hundred affected individuals and seeks the suitable dose range. Phase 3 is the decisive stage: several thousand participants, randomised, blinded, placebo-controlled, over longer periods — only here does it become clear whether a substance delivers what earlier data promised, and which adverse effects occur at what frequency.
The distance between “GLP-3” and “GLP-5” is therefore not a generational leap but the difference between a substance with robust data from more than 2,000 people and a substance that has so far been examined only in rats.
Legal status in Germany
Semaglutide, liraglutide, dulaglutide, tirzepatide and teduglutide are approved, prescription-only medicinal products. They must be prescribed by a physician and obtained through pharmacies. Advertising prescription-only medicinal products to the general public is not permitted under German medicines advertising law.
Retatrutide, NA-931 and VRX-0075 are not approved — in any country. They are therefore not marketable medicinal products. Outside authorised clinical trials they exist solely as reference and research material for scientific laboratory purposes.
Consumer protection organisations have for some time pointed out that advertising in the environment of this substance class makes impermissible health-related claims. This concerns in particular offers that link unapproved substances with statements about weight reduction.
Frequently asked questions
Does GLP-5 exist as an active substance?
No. “GLP-5” is not a scientific substance designation but a shorthand that arose on the grey market for VRX-0075, a quintuple agonist at the preclinical stage. No hormone of that name exists in human physiology.
Does a higher number mean better efficacy?
No. The number describes only the count of receptors addressed. Whether more receptors lead to better results is an empirical question that has to be answered for each substance individually in clinical trials. For “GLP-4” and “GLP-5”, the data required for that are not available.
Why is tirzepatide called “GLP-2”?
Because the grey-market nomenclature counts receptors and tirzepatide acts on two. The designation collides with the actual hormone GLP-2 and is technically inaccurate. In the scientific literature tirzepatide is described as a dual GIP/GLP-1 receptor agonist.
What does “research use only” mean in this context?
The labelling denotes material intended exclusively for scientific laboratory purposes. It is not a restriction on the formulation but a legal category: such material is not a medicinal product, is not subject to pharmaceutical quality testing for use in humans, and may be applied neither to humans nor to animals.
How can reliable statements on development status be recognised?
By verifiable primary sources: registered trials in public trial registers, peer-reviewed published articles, congress abstracts with a number and year, and announcements from regulatory authorities. Statements without such evidence — particularly timelines for supposedly imminent approvals — should be treated critically.
Important notice
This page serves solely to classify development and approval status scientifically. It does not constitute health advice, recommends no substance, describes no application and replaces no medical consultation. Information on trial dosing reflects exclusively the design of published clinical studies conducted under medical supervision and is not transferable to other situations.
All substances offered by Peptélia are intended exclusively for scientific use in the laboratory (research use only). They are not medicinal products, not food supplements and not cosmetics. Application in humans or animals, as well as diagnostic or therapeutic use, is expressly excluded.
Approved medicinal products containing semaglutide, liraglutide, dulaglutide, tirzepatide or teduglutide are prescription-only and are not distributed by Peptélia. Anyone considering medical treatment for overweight or metabolic disease should consult a physician.
Sources: American Journal of Managed Care, Retatrutide Achieves Up to 30.3% Average Weight Loss in Phase 3 TRIUMPH-1 Trial, 21 May 2026 · Eli Lilly and Company, press release on the TRIUMPH-1 trial, May 2026 · American Diabetes Association, 86th Scientific Sessions, poster 2839-LB, 7 June 2026 · Biomed Industries, phase 2 results for NA-931, EASD congress Vienna, September 2025 · European Medicines Agency, approval information on semaglutide, tirzepatide and teduglutide · Verbraucherzentrale, notes on GLP-1-related advertising.
As of: September 2026 · The development status may change; this page is updated when there are relevant developments.
For research use only. Not for use in or on the human body.
