Comparisons

GLP-3 vs GLP-1: what the nickname means and how the drugs compare

Updated by the GLP Ladder Editorial Team. Editorial policy.

Short answer

GLP-3 is not a hormone or drug class, just an online nickname for retatrutide, an investigational drug acting on three receptors: GIP, GLP-1 and glucagon. Semaglutide acts on one, tirzepatide on two. In separate trials, retatrutide 12 mg averaged −25.0% at 80 weeks, semaglutide 2.4 mg −14.9% at 68 weeks. Not approved anywhere, as of Oct 19, 2026.

On this page9 sections
  1. Receptor targets by drug
  2. Where the name comes from
  3. The three receptors in plain terms
  4. Is GLP-3 better than GLP-1?
  5. Side effects across the three classes
  6. Half-life: all three are weekly
  7. Why the nickname is a warning sign
  8. FAQ
  9. Sources
Key facts (as of Oct 19, 2026)
ItemValueSource
What GLP-3 meansSeller and community nickname for retatrutide; not a hormone or drug classFDA, Aug 24, 2026
Retatrutide receptor targetsGIP, GLP-1 and glucagon receptors (triple agonist)Cell Metabolism, Aug 18, 2022
Tirzepatide receptor targetsGIP and GLP-1 receptors (dual agonist)Eli Lilly, May 13, 2022
Semaglutide receptor targetGLP-1 receptor onlyNovo Nordisk, Jun 18, 2026
Retatrutide statusNot approved by any regulator; U.S. submission planned Q1 2027Eli Lilly, Sep 29, 2026
FDA warning letter naming GLP-3RAug 24, 2026: retatrutide sold as GLP-3R called an unapproved new drugFDA, Aug 24, 2026
Triple agonist trial resultRetatrutide 12 mg −25.0% at 80 weeks (TRIUMPH-1, treatment-regimen estimand)N Engl J Med, Sep 29, 2026
Dual agonist trial resultTirzepatide 15 mg −20.9% at 72 weeks (SURMOUNT-1, treatment-regimen estimand)N Engl J Med, Jul 21, 2022
GLP-1 agonist trial resultSemaglutide 2.4 mg −14.9% at 68 weeks (STEP 1, treatment-policy estimand)New England Journal of Medicine, Mar 18, 2021
Dual vs GLP-1 head-to-headSURMOUNT-5: tirzepatide −20.2% vs semaglutide −13.7% at 72 weeksN Engl J Med, Jul 3, 2025

Also useful: Semaglutide overview, GLP-1 level plotter (all compounds), Retatrutide level plotter, Tirzepatide level plotter.

“GLP-3” shows up in forums, social media and on websites selling unapproved peptides. It sounds like the next generation after GLP-1 drugs such as Ozempic and Wegovy. It is not a scientific term. In practice it means one drug, retatrutide, an investigational Eli Lilly molecule that acts on three hormone receptors. The table below shows what each class targets. For the drug itself, see the retatrutide hub; for the approved drugs it is compared with, see the tirzepatide hub and the semaglutide hub.

Receptor targets by drug

Which receptors each drug activates, and its status as of Oct 19, 2026
DrugBrand namesGLP-1 receptorGIP receptorGlucagon receptorStatus
SemaglutideWegovy, OzempicYesNoNoFDA approved
TirzepatideZepbound, MounjaroYesYesNoFDA approved
Retatrutide (“GLP-3”)NoneYesYesYesInvestigational; not approved anywhere

Sources: Wegovy label (Novo Nordisk, Jun 18, 2026), Lilly’s Mounjaro approval release (Eli Lilly, May 13, 2022), retatrutide pharmacology (Cell Metabolism, Aug 18, 2022), retatrutide status (Eli Lilly, Aug 12, 2026).

The pattern is simple: one receptor, two receptors, three receptors. “GLP-3” is shorthand for “the three-receptor one”. Lilly does not use the name. Its releases call retatrutide a triple agonist (Eli Lilly, May 21, 2026).

Where the name comes from

GLP-1 is a real hormone: glucagon-like peptide-1, released by the gut after eating. Drugs that activate its receptor are called GLP-1 receptor agonists, usually shortened to GLP-1s. Because that short name became the everyday label for the whole category, a drug that adds more receptors invited a bigger number. The 3 counts receptors, not hormones. No hormone called GLP-3 is involved in how retatrutide works.

The nickname also appears in regulatory documents, because sellers use it. FDA’s Aug 24, 2026 warning letter to Peak Performance Peptides describes retatrutide sold as “GLP-3R” and calls it an unapproved new drug (FDA, Aug 24, 2026). A Mar 31, 2026 letter to Gram Peptides describes retatrutide sold as “GLP-1-R peptide” (FDA, Mar 31, 2026). Renaming does not change the legal status: the product is still retatrutide, and it is still unapproved.

The three receptors in plain terms

  • GLP-1 receptor. The target of all current GLP-1 drugs. Activating it affects appetite and blood sugar.
  • GIP receptor. GIP (glucose-dependent insulinotropic polypeptide) is a second gut hormone released after meals. Tirzepatide was the first approved drug to target both GIP and GLP-1 receptors (Eli Lilly, May 13, 2022).
  • Glucagon receptor. Glucagon is a pancreatic hormone. Retatrutide is the only one of the three drugs that activates this receptor. In laboratory testing it showed balanced glucagon and GLP-1 receptor activity with more GIP receptor activity (Cell Metabolism, Aug 18, 2022).

More receptors does not automatically mean better. Each added target brings its own effects, and only trials can show the balance of benefit and harm.

Is GLP-3 better than GLP-1?

On average weight loss in trials, the three-receptor drug has reported the largest numbers. But the drugs have mostly been tested in separate trials, so the comparison is indirect.

Top-dose weight change in each drug’s pivotal obesity trial (intention-to-treat-style estimands)
ClassDrug and doseTrialTimepointWeight changePlacebo
GLP-1Semaglutide 2.4 mgSTEP 168 weeks−14.9%−2.4%
DualTirzepatide 15 mgSURMOUNT-172 weeks−20.9%−3.1%
TripleRetatrutide 12 mgTRIUMPH-180 weeks−25.0%−3.9%

Sources: (New England Journal of Medicine, Mar 18, 2021) (N Engl J Med, Jul 21, 2022) (N Engl J Med, Sep 29, 2026)

STEP 1 used a treatment-policy estimand; SURMOUNT-1 and TRIUMPH-1 used treatment-regimen estimands. Both kinds count everyone randomized. Lilly’s press release reports retatrutide 12 mg as −28.3% under the efficacy estimand, which assumes everyone stayed on treatment (Eli Lilly, May 21, 2026). The trials differ in length (68, 72 and 80 weeks), population and era, so the steps in this table are not clean measures of the extra receptor.

Only one step of the ladder has a randomized head-to-head result. In SURMOUNT-5, tirzepatide averaged −20.2% vs −13.7% for semaglutide at 72 weeks in 751 adults with obesity (N Engl J Med, Jul 3, 2025). The next step, triple vs dual, is being tested in TRIUMPH-5 (NCT06662383), which compares retatrutide with tirzepatide and had no results as of Oct 19, 2026 (ClinicalTrials.gov, Jul 20, 2026).

“Better” also includes things trials of weight loss do not settle:

  • Approval and supply. Semaglutide and tirzepatide are FDA-approved medicines with labels, quality controls and prescribers. Retatrutide is legally available only in Lilly trials.
  • Outcome evidence. Semaglutide lowered major cardiovascular events in SELECT (6.5% vs 8.0%, hazard ratio 0.80) (New England Journal of Medicine, Dec 14, 2023). Retatrutide has no completed outcomes trial.
  • Tolerability. Discontinuation for side effects reached 11.3% on retatrutide 12 mg vs 4.9% on placebo in TRIUMPH-1 (Eli Lilly, May 21, 2026), compared with 6.2% vs 2.6% on tirzepatide 15 mg in SURMOUNT-1 (N Engl J Med, Jul 21, 2022).

Side effects across the three classes

Selected adverse events at the top dose vs placebo (different trials and pools)
Adverse eventSemaglutide 2.4 mg (Wegovy label)Tirzepatide 15 mg (Zepbound label)Retatrutide 12 mg (TRIUMPH-1)
Nausea44% vs 16%28% vs 8%42.4% vs 14.8%
Vomiting24% vs 6%13% vs 2%25.3% vs 4.8%
Diarrhea30% vs 16%23% vs 8%32.0% vs 13.5%
Dysesthesia2% vs 1%Not in label table12.5% vs 0.9%

Sources: (Novo Nordisk, Jun 18, 2026) (DailyMed, Aug 28, 2026) (Eli Lilly, May 21, 2026)

All three mainly cause gastrointestinal effects. Dysesthesia, meaning abnormal skin sensations such as tingling or burning, is the signal most associated with retatrutide; it reached 20.9% on 12 mg vs 0.7% on placebo in TRIUMPH-4 (Eli Lilly, Dec 11, 2025). The Wegovy label reports it at 22% on the 7.2 mg dose, so it is not exclusive to the triple agonist.

Half-life: all three are weekly

Half-lives and model accumulation (GLP Ladder one-compartment model)
DrugPublished half-lifeFraction of a dose left after 7 days (model)Weekly accumulation ratio (model)
SemaglutideApproximately 1 week0.50002.0000
TirzepatideAbout 5 days (Zepbound label: 5–6 days)0.37891.6101
RetatrutideApproximately 6 days0.44541.8033

Sources: (Novo Nordisk, Jun 18, 2026) (DailyMed, Aug 28, 2026) (The Lancet, Oct 27, 2022)

Half-life sets how levels build up between weekly doses; it does not measure strength. The model output is a relative amount, not a blood level. You can overlay all three in the multi-compound plotter or open each one in the retatrutide plotter, tirzepatide plotter and semaglutide plotter.

Why the nickname is a warning sign

The name “GLP-3” mostly appears where retatrutide is sold outside trials. FDA has written to sellers of “research use only” retatrutide since at least Dec 10, 2024 (FDA, Dec 10, 2024), and has said compounded retatrutide does not qualify for the compounding exemptions (FDA, Sep 9, 2025). On Aug 12, 2026, Lilly announced six U.S. lawsuits and said it had reported more than 14,000 listings across more than 100 countries (Eli Lilly, Aug 12, 2026). Lilly states that retatrutide cannot be legally sold or marketed for human use (Eli Lilly, Sep 29, 2026).

A product labeled GLP-3 is not a newer class of medicine. It is not the product tested in Lilly’s trials, and no regulator has checked what it contains. For approval status and timeline, see is retatrutide FDA approved. For the trial-by-trial numbers, see retatrutide trial results and the three-way comparison.

Frequently asked questions

What is GLP-3 retatrutide?

GLP-3 is a nickname used online and by unapproved sellers for retatrutide (LY3437943), an investigational Eli Lilly drug. Retatrutide activates three receptors: GIP, GLP-1 and glucagon. The 3 refers to that count of receptors. Lilly calls it a triple agonist, not GLP-3. FDA warning letters show sellers marketing it as GLP-3R. It is not approved anywhere as of Oct 19, 2026.

Is GLP-3 better than GLP-1?

There is no head-to-head trial of retatrutide vs a GLP-1-only drug in obesity. In separate trials, retatrutide 12 mg averaged −25.0% at 80 weeks and semaglutide 2.4 mg −14.9% at 68 weeks, both under intention-to-treat-style estimands. Trials differ in length and population. Semaglutide also has an FDA approval and a proven heart-outcome benefit; retatrutide has neither yet. Better depends on more than average weight loss.

Is GLP-3 a real hormone?

No. GLP-1 (glucagon-like peptide-1) is a real gut hormone, and the GLP-1 drugs are named after it. No hormone called GLP-3 is involved in how retatrutide works. The name counts receptors: GLP-1 drugs hit one, tirzepatide hits two and retatrutide hits three. It is a marketing shorthand, not a scientific term.

Is GLP-3 FDA approved?

No. Lilly said on Aug 12, 2026 that no retatrutide medicine has been approved by any regulator, and on Sep 29, 2026 that it plans a U.S. submission in the first quarter of 2027. Products sold as GLP-3 or research-use retatrutide are not the trial drug, and FDA has sent warning letters calling them unapproved new drugs.

Is GLP-3 the same as tirzepatide?

No. Tirzepatide (Zepbound, Mounjaro) is an FDA-approved dual agonist that acts on GIP and GLP-1 receptors. Retatrutide, the drug nicknamed GLP-3, adds the glucagon receptor. Both are Eli Lilly molecules, and Lilly is comparing them directly in TRIUMPH-5 (NCT06662383), which had no results as of Oct 19, 2026.

What is the difference between GLP-1, dual and triple agonists?

A GLP-1 receptor agonist such as semaglutide acts on one receptor. A dual agonist such as tirzepatide acts on GIP and GLP-1 receptors. A triple agonist such as retatrutide acts on GIP, GLP-1 and glucagon receptors. All three are once-weekly peptides, with half-lives of about 6 days for retatrutide, about 5 days for tirzepatide and about 1 week for semaglutide.

Sources

  1. Warning Letter: Peak Performance Peptides, MARCS-CMS 735127. U.S. Food and Drug Administration, Aug 24, 2026. Accessed Oct 19, 2026.
  2. Warning Letter: Gram Peptides, MARCS-CMS 721806. U.S. Food and Drug Administration, Mar 31, 2026. Accessed Oct 19, 2026.
  3. Warning Letter: Prime Vitality, Inc. dba Prime Peptides, MARCS-CMS 695156. U.S. Food and Drug Administration (CDER), Dec 10, 2024. Accessed Oct 19, 2026.
  4. Warning Letter: ASN-LABS, MARCS-CMS 716459. U.S. Food and Drug Administration, Sep 9, 2025. Accessed Oct 19, 2026.
  5. Lilly calls on online platforms, payment companies and regulators to shut down the illegal retatrutide black market. Eli Lilly and Company (via PR Newswire), Aug 12, 2026. Accessed Oct 19, 2026.
  6. Lilly's triple agonist, retatrutide, delivered substantial weight loss and A1C reduction, underscoring its potential promise for people with obesity and type 2 diabetes. Eli Lilly and Company (via PR Newswire; also investor.lilly.com), Sep 29, 2026. Accessed Oct 19, 2026.
  7. Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. Eli Lilly and Company (via PR Newswire; also investor.lilly.com), May 21, 2026. Accessed Oct 19, 2026.
  8. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med (abstract via PubMed PMID 42814954; doi:10.1056/NEJMoa2604169), Sep 29, 2026. Accessed Oct 19, 2026.
  9. Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial. Eli Lilly and Company (via PR Newswire), Dec 11, 2025. Accessed Oct 19, 2026.
  10. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metabolism 2022;34(9):1234-1247.e9 (abstract via PubMed PMID 35985340; doi:10.1016/j.cmet.2022.07.013), Aug 18, 2022. Accessed Oct 19, 2026.
  11. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. The Lancet 2022;400(10366):1869-1881 (abstract via PubMed PMID 36354040; doi:10.1016/S0140-6736(22)02033-5), Oct 27, 2022. Accessed Oct 19, 2026.
  12. A Study of Retatrutide (LY3437943) Compared to Tirzepatide (LY3298176) in Adults Who Have Obesity (TRIUMPH-5). ClinicalTrials.gov (U.S. NLM), Jul 20, 2026. Accessed Oct 19, 2026.
  13. FDA approves Lilly's Mounjaro™ (tirzepatide) injection, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes. Eli Lilly and Company (investor.lilly.com), May 13, 2022. Accessed Oct 19, 2026.
  14. ZEPBOUND (tirzepatide) injection, for subcutaneous use - Full Prescribing Information, Medication Guide and Instructions for Use (DailyMed SPL set ID 487cd7e7-434c-4925-99fa-aa80b1cc776b, version 40). U.S. National Library of Medicine (DailyMed) / Eli Lilly and Company, Aug 28, 2026. Accessed Oct 19, 2026.
  15. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387(3):205-216 (Jastreboff AM et al.; PubMed PMID 35658024; doi:10.1056/NEJMoa2206038), Jul 21, 2022. Accessed Oct 19, 2026.
  16. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med 2025;393(1):26-36 (Aronne LJ et al.; PubMed PMID 40353578; doi:10.1056/NEJMoa2416394), Jul 3, 2025. Accessed Oct 19, 2026.
  17. WEGOVY (semaglutide) injection, for subcutaneous use; WEGOVY (semaglutide) tablets, for oral use - Full Prescribing Information (SPL, Revised 6/2026). Novo Nordisk / National Library of Medicine DailyMed, Jun 18, 2026. Accessed Oct 19, 2026.
  18. Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine (Wilding JPH et al.; PMID 33567185), Mar 18, 2021. Accessed Oct 19, 2026.
  19. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine (Lincoff AM et al.; PMID 37952131), Dec 14, 2023. Accessed Oct 19, 2026.

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