GLP-1 vs GLP-2 vs GLP-3: what each one really is

Glucagon-like peptide 3 isn’t a human hormone. People make two glucagon-like peptides, GLP-1 and GLP-2, and the “GLP-3” you see in videos and on seller sites is a nickname for retatrutide, an investigational weight-loss injection from Eli Lilly that acts on three hormone receptors. As of October 2026, retatrutide isn’t approved anywhere, and it can’t be legally prescribed or sold in the US.

That makes GLP-1, GLP-2 and “GLP-3” three different kinds of thing: a hormone with many approved drugs, a hormone with one gut-disease drug, and a trial drug. Here’s what each one is.

GLP-1, GLP-2 and “GLP-3” at a glance

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Sources: Physiological Reviews, Peptides, the Gattex label and TRIUMPH-1.

Where GLP-1 and GLP-2 come from

Both hormones are cut from one larger protein called proglucagon. A 2026 review in Physiological Reviews lists the family: glucagon, GLP-1, GLP-2 and oxyntomodulin. Each acts through its own receptor, and together they touch blood sugar, fat and protein metabolism, appetite, nutrient absorption and gut movement.

GLP-1 and GLP-2 are released together by L cells in the intestine, according to a 2024 review. From there they go separate ways.

GLP-1 vs GLP-2

GLP-1 is the one behind today’s diabetes and weight-loss drugs. The Physiological Reviews authors credit GLP-1 drugs with glucose-lowering, appetite-suppressing and cardiovascular effects. FDA-approved drugs that act on the GLP-1 receptor include:

• Semaglutide, as Ozempic for type 2 diabetes and Wegovy for weight reduction (Wegovy label).
• Tirzepatide, which also acts on the GIP receptor, as Mounjaro for type 2 diabetes and Zepbound for weight reduction and sleep apnea (Zepbound label).
• Orforglipron, a daily pill sold as Foundayo for weight reduction, approved in 2026 (Foundayo label).

When the FDA approved Zepbound, it described the drug as activating receptors for hormones “secreted from the intestine” to “reduce appetite and food intake” (FDA). Every one of these drugs carries a boxed warning for thyroid C-cell tumors.

GLP-2 works mainly on the gut itself. In people, it makes the intestinal lining grow, strengthens the gut barrier and increases blood flow to the intestine, and it doesn’t seem to reduce appetite or food intake (Peptides, 2024). Teduglutide, sold as Gattex, is a GLP-2 drug approved in 2012 for adults and children 1 year and older with short bowel syndrome who depend on IV nutrition or fluids. Its label explains that GLP-2 is “secreted by L-cells of the distal intestine” and increases intestinal blood flow. The label also warns that it may speed the growth of tumors, so adults have a colonoscopy and upper endoscopy before starting and again after a year.

The 2024 review suggests GLP-2’s gut-barrier effect, which reduced inflammation in obese rodents, might be worth pairing with GLP-1 drugs one day. That idea is early, and no GLP-2 drug is approved for weight loss.

The real GLP-3: a shark hormone

There is a peptide that scientists call glucagon-like peptide 3, but not in people. Chondrichthyans, the group that includes sharks, rays and chimaeras, make a third proglucagon-derived peptide, GLP-3, “in addition to GLP-1 and GLP-2 that occur in other vertebrates,” according to a 2024 study in General and Comparative Endocrinology.

That study perfused the gut and liver of the Pacific spiny dogfish, a small shark, with GLP-3 for 15 minutes. It saw no change in glucose or fat uptake in the gut, but the liver switched from making ketones to using them. The authors say its actions differ from those of GLP-1 in bony fish. It has nothing to do with weight-loss drugs.

“GLP-3” online means retatrutide

When someone online says GLP-3, they nearly always mean retatrutide. It’s an informal shorthand, not a hormone name: retatrutide is a single lab-made molecule that activates the GIP, GLP-1 and glucagon receptors at once, which is why Lilly calls it a triple hormone receptor agonist. For comparison, semaglutide acts on one of those receptors and tirzepatide on two.

Retatrutide is investigational. In TRIUMPH-1, published in the New England Journal of Medicine in September 2026, Lilly randomly assigned 2,339 adults with obesity and without diabetes to weekly injections of retatrutide at 4 mg, 9 mg or 12 mg, or placebo, for 80 weeks. The trial measured percent change in body weight, and in smaller groups, knee osteoarthritis pain and sleep apnea events. Counting everyone assigned, average weight change was:

The paper reports gastrointestinal events as the most common adverse events. These are trial doses, not a prescribing plan, and the full safety picture won’t be set out unless the FDA reviews an application. Lilly funded the trial, and several authors work for Lilly.

GLP-1 drugs vs “GLP-3”: how the trials compare

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Sources: the Wegovy, Foundayo and Zepbound labels and TRIUMPH-1. All four figures count everyone assigned to the drug.

These were separate trials with different lengths and volunteers, so the table isn’t a ranking. The direct test is TRIUMPH-5, a Lilly trial randomly assigning about 800 adults with obesity to retatrutide or tirzepatide. When we checked on October 27, 2026, it was active and no longer recruiting, with an estimated primary completion date of November 2026 and no results posted. Our tirzepatide vs retatrutide guide goes deeper.

Is “GLP-3” legal to buy?

No. In August 2026, Lilly stated that “no medicine containing retatrutide has yet been approved for human use by any regulatory agency in the world” and that “it cannot be sold to consumers.” Lilly also cites the FDA’s position that sales of unapproved retatrutide to consumers are illegal, that it “cannot be lawfully compounded,” and that products labeled research-use-only “are of unknown quality and may be harmful.”

So a vial sold as “GLP-3” has had no FDA review of what’s in it, how much, or how clean it is. We don’t list or link to any seller of retatrutide. The legal routes today are a clinical trial or, for some adults with severe obesity and serious complications, a physician’s request to Lilly’s expanded access program; our how to get retatrutide guide explains both.

When could retatrutide be approved?

Lilly says it plans to submit a Biologics License Application to the FDA in the first quarter of 2027. That’s a plan to apply, not an approval, and Lilly hasn’t given an approval or launch date. Until then, any claim that “GLP-3” is FDA-approved or available by prescription is wrong.

Approved options now

If you want a GLP-1 medicine today, the approved choices include the weekly injections Zepbound and Wegovy and the daily pills Foundayo and the Wegovy pill. Our semaglutide vs tirzepatide guide and Foundayo vs Zepbound guide compare them, and our peptides vs GLP-1 guide explains how these drugs differ from the peptides sold online.

The bottom line

GLP-1 and GLP-2 are real human gut hormones made from proglucagon. GLP-1 drugs treat type 2 diabetes and obesity; the GLP-2 drug teduglutide treats short bowel syndrome. GLP-3 is a hormone only in sharks and their relatives. The “GLP-3” sold online is retatrutide, a Lilly trial drug that averaged up to 25.0% weight loss over 80 weeks in TRIUMPH-1, isn’t approved anywhere, and can’t be legally compounded or sold. Talk to a licensed clinician about the approved options on our weight-loss hub.