GLP-3 (Retatrutide): What It Is, How It Compares to Tirzepatide, and When It's Expected
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Short answer: "GLP-3" is a nickname for retatrutide, an investigational once-weekly injection from Eli Lilly that acts on three hormone receptors: GIP, GLP-1 and glucagon.[1] It is not approved anywhere. Lilly said on July 23, 2026 that it plans to submit it to the FDA in the first quarter of 2027.[2] In its largest published trial, body weight fell by an average of 25.0% over 80 weeks on the top dose, against 3.9% on placebo.[1]
This page sets out what is known as of November 13, 2026: what the name means, how retatrutide differs from semaglutide and tirzepatide, what each trial found, what went wrong for participants, where approval stands, and why "research" vials sold online are a bad idea. It ends with the part that applies to anyone on any of these medications today: eating enough when appetite is small, which is the subject of our guide to what to eat when you're eating less.
General information, not medical advice. Retatrutide can only be taken legally inside a clinical trial or Lilly's expanded-access program. Talk to your prescriber about any medication decision.
What does "GLP-3" mean?
"GLP-3" is an informal name, not an official drug class. The published trials and Lilly describe retatrutide as a triple agonist: one molecule that activates the receptors for three gut and pancreatic hormones, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon.[1][3] The "3" in the nickname counts receptors. People use it because the medications before it line up the same way:
- Semaglutide (Wegovy, Ozempic) acts on one receptor, GLP-1.[4]
- Tirzepatide (Zepbound, Mounjaro) acts on two, GIP and GLP-1.[5]
- Retatrutide adds a third, the glucagon receptor. Its development code was LY3437943.[6]
You will not find "GLP-3" on a label, in a trial registry or in the journals. If a product is sold as "GLP-3", that name alone tells you it is not an approved medicine, because no approved medicine carries it.
How is retatrutide different from semaglutide and tirzepatide?
| Medication | Receptors targeted | Dosing | US status (November 2026) | Headline obesity trial |
|---|---|---|---|---|
| Semaglutide (Wegovy; Ozempic for type 2 diabetes) | GLP-1 | Once-weekly injection; Wegovy also comes as a tablet | FDA-approved | STEP 1: body weight −14.9% at 68 weeks on 2.4 mg, vs −2.4% on placebo[7] |
| Tirzepatide (Zepbound; Mounjaro for type 2 diabetes) | GIP and GLP-1 | Once-weekly injection | FDA-approved | SURMOUNT-1: −20.9% at 72 weeks on 15 mg, vs −3.1% on placebo[8] |
| Retatrutide ("GLP-3") | GIP, GLP-1 and glucagon | Once-weekly injection in trials | Not approved; FDA submission planned for Q1 2027 | TRIUMPH-1: −25.0% at 80 weeks on 12 mg, vs −3.9% on placebo[1] |
Sources: the FDA labels for status and dosing,[4][5] Lilly for the planned submission,[2] and each trial's published paper. All three trial figures are treatment-regimen results, which count everyone randomized whether or not they kept taking the drug.
Read the last column with care. These are three different trials, with different people, lengths and doses, so the numbers cannot be lined up as a contest. No trial comparing retatrutide with tirzepatide directly has reported results. The only head-to-head result so far is against semaglutide in type 2 diabetes (TRANSCEND-T2D-2, below), which Lilly described as the first phase 3 trial comparing retatrutide with another incretin medicine.[9]
Tirzepatide is also a Lilly medication, and what to eat while taking it is covered in what to eat on Zepbound.
What have the retatrutide trials found?
Two kinds of result exist, and the difference matters. Peer-reviewed papers have been checked by outside reviewers and give full methods. Topline results come from a Lilly press release, before any journal has checked them. Both are marked below.
Phase 2 (peer-reviewed, 2023)
- Obesity, 338 adults, 48 weeks. Doses from 1 to 12 mg a week. At 48 weeks, the average change in body weight was −8.7% on 1 mg, −17.1% on 4 mg, −22.8% on 8 mg and −24.2% on 12 mg, against −2.1% on placebo.[6]
- Type 2 diabetes, 281 adults, 36 weeks. At 24 weeks, HbA1c fell by 2.02 points on 12 mg, against 0.01 on placebo and 1.41 on dulaglutide 1.5 mg, an approved GLP-1 medication. At 36 weeks, body weight fell by 16.94% on 12 mg, against 3.00% on placebo.[10]
Phase 3, the TRIUMPH program (2025–2026)
| Trial | Who took part | Length and doses | Main body weight result | Status of the data |
|---|---|---|---|---|
| TRIUMPH-1 | 2,339 adults with obesity, without diabetes | 80 weeks; 4, 9 or 12 mg | −17.6%, −23.7% and −25.0% vs −3.9% on placebo[1] | Peer-reviewed, NEJM, November 2026 |
| TRIUMPH-2 | 1,152 adults with obesity and type 2 diabetes | 80 weeks; 4, 9 or 12 mg | −11.9%, −16.8% and −18.8% vs −5.1%[3] | Peer-reviewed, Lancet, October 2026 |
| TRIUMPH-3 | 1,949 adults with a BMI of 35 or more and established heart disease | 80 weeks; 9 or 12 mg | −21.6% and −22.6% vs −3.2%[2] | Topline, Lilly release, July 23, 2026 |
| TRIUMPH-4 | 445 adults with obesity and knee osteoarthritis | 68 weeks; 9 or 12 mg | −20.0% and −23.7% vs −4.6%[11] | Peer-reviewed, NEJM, November 2026 |
| TRANSCEND-T2D-2 | 1,298 adults with type 2 diabetes on metformin | 80 weeks; 9 or 12 mg vs semaglutide 2 mg, open-label | −19.5% and −20.9% vs −9.4% on semaglutide[9] | Topline, Lilly release, October 28, 2026 |
The TRIUMPH-3 and TRANSCEND-T2D-2 figures are Lilly's "efficacy estimand", which estimates the effect in people who kept taking the drug, and runs higher than the treatment-regimen figures in the published papers. In TRIUMPH-1, for example, the 12 mg result was −28.3% by Lilly's efficacy estimand and −25.0% by the treatment-regimen estimand in the journal.[12][1]
Beyond body weight, the trials measured other outcomes:
- Blood sugar. In TRIUMPH-2, HbA1c fell by 1.4 to 1.6 points from a starting average of 7.7%, against 0.2 on placebo (topline).[2] In TRANSCEND-T2D-2 it fell by 2.2 points on both retatrutide doses, against 1.8 on semaglutide 2 mg, from an average of 8.3%.[9]
- Knee pain. In TRIUMPH-4, the WOMAC knee pain score (0 to 10) fell by 3.96 and 3.74 points on 9 and 12 mg, against 2.12 on placebo.[11]
- Sleep apnea. In people with moderate-to-severe obstructive sleep apnea and no diabetes, breathing interruptions fell by 34.3 and 31.7 events an hour on 9 and 12 mg, against 9.9 on placebo, from a starting average of 58.6.[13]
- Heart outcomes. Not settled. A dedicated trial, TRIUMPH-Outcomes, aims to enroll about 10,000 adults and is not expected to finish until February 2029, by its registry entry.[14]
Retatrutide side effects reported in trials
The pattern is the one people on semaglutide and tirzepatide will recognize, mostly in the gut and rising with the dose, plus two findings worth knowing about.
Digestive symptoms were the most common, and dose-related. In phase 2 they were mostly mild to moderate and were partly reduced by starting at 2 mg rather than 4 mg.[6] In TRIUMPH-1, as reported in Lilly's topline release:[12]
| Reported event, TRIUMPH-1 | 4 mg | 9 mg | 12 mg | Placebo |
|---|---|---|---|---|
| Nausea | 28.6% | 38.4% | 42.4% | 14.8% |
| Diarrhea | 25.2% | 34.1% | 32.0% | 13.5% |
| Constipation | 23.8% | 25.9% | 26.1% | 10.9% |
| Vomiting | 10.6% | 22.8% | 25.3% | 4.8% |
| Dysesthesia (abnormal skin sensations) | 5.1% | 12.3% | 12.5% | 0.9% |
| Urinary tract infection | 7.5% | 8.8% | 8.4% | 5.3% |
| Stopped the drug because of an adverse event | 4.1% | 6.9% | 11.3% | 4.9% |
Rates were lower in the people with type 2 diabetes in TRIUMPH-2: nausea in 14%, 21% and 28% on the three doses, against 8% on placebo, and diarrhea in 27%, 34% and 34%, against 13%.[3]
Dysesthesia is the new one. It means unusual skin sensations, such as tingling or sensitivity. It was rare on placebo and more common on retatrutide in every trial that reported it: 4% to 7% in TRIUMPH-2,[3] 6.4% on both doses in TRIUMPH-3,[2] and 8.8% and 20.9% in TRIUMPH-4.[15] Lilly reported that it was generally mild to moderate, mostly resolved during treatment, and that most participants kept taking the drug.[12]
Other findings.
- Heart rate. In phase 2, heart rate rose with the dose, peaked at 24 weeks and declined after that.[6]
- Low blood pressure. In TRIUMPH-2, hypotension was reported in 1%, 5% and 6% on the three doses, against under 1% on placebo.[3]
- Urinary tract infections were somewhat more common than on placebo in TRIUMPH-1, as in the table above.[12]
- Serious adverse events were more common with retatrutide than with placebo in the two knee osteoarthritis trials.[11]
How many people stopped. Stopping the drug because of an adverse event ranged from about 4% to 13.5% across doses in TRIUMPH-1 to TRIUMPH-3, against about 5% on placebo.[12][3][2] It reached 12.2% and 18.2% in TRIUMPH-4, against 4.0%, where most participants started with a BMI of 35 or more and discontinuation tracked starting BMI.[15] For comparison, 6.2% stopped tirzepatide 15 mg for an adverse event in SURMOUNT-1, against 2.6% on placebo.[8]
Trials exclude many people and watch participants closely, so real-world experience can differ. Anyone in a trial who has symptoms should tell the study team; anyone on an approved GLP-1 who cannot keep fluids down should call their prescriber. Food-first approaches for unsettled days are in what to eat on queasy days.
When will retatrutide be approved?
It is not approved by the FDA or any other regulator as of November 13, 2026. The dated record, as reported by each source:
- December 11, 2025: Lilly reports the first phase 3 topline result, TRIUMPH-4, and says more results are expected in 2026.[15]
- May 21, 2026: TRIUMPH-1 topline. Lilly states that retatrutide is investigational and legally available only to participants in its trials.[12]
- July 23, 2026: TRIUMPH-2 and TRIUMPH-3 topline. Lilly says it is completing the chemistry, manufacturing and controls package for a Biologics License Application and plans to submit to the FDA in the first quarter of 2027.[2]
- August 2026: Lilly's pre-approval expanded access program is listed as available on ClinicalTrials.gov. It is for single patients aged 18 or older with a BMI of 35 or more, two or more serious obesity-related complications, obesity that persists despite the highest available dose of an approved treatment, and no way to join a trial. A physician requests it.[16]
- September to November 2026: TRIUMPH-1, TRIUMPH-2, TRIUMPH-4 and the sleep apnea results are published in the New England Journal of Medicine and The Lancet.[1][3][11][13]
- October 28, 2026: TRANSCEND-T2D-2 topline, against semaglutide.[9]
So the earliest milestone on record is a submission in early 2027. A submission is not an approval: the FDA then has to evaluate the application, and neither Lilly nor the FDA has given a decision date. Any approval date you see quoted is someone's estimate. Lilly's releases describe a US submission; we found no announced filing in other countries as of this date.
Is it safe to buy "research" retatrutide online?
No. Here is why.
- It is illegal to sell it to you. The FDA has warned companies selling unapproved drugs containing retatrutide that are "falsely labeled 'for research purposes' or 'not for human consumption'", sold directly to consumers with dosing instructions. It "urges consumers not to purchase these products which are of unknown quality and may be harmful to their health."[17]
- It cannot be compounded legally either. The FDA says retatrutide cannot be used in compounding under federal law, and has warned telehealth companies, ingredient distributors and outsourcing facilities over it.[17]
- Nobody can tell you what is in the vial. Unapproved products sold online may be counterfeit, contain the wrong ingredients, or contain too little, too much or none of the active ingredient, the FDA says.[17] Lilly calls them "entirely unverified, unapproved", says no retatrutide medicine has been approved by any regulator, and announced six lawsuits against US sellers on August 12, 2026.[18]
- Harm is already being reported. A 2026 case report describes a woman in her mid-20s admitted to hospital with five days of persistent nausea and repeated vomiting after four weekly injections of a product reported to contain retatrutide, given in a wellness setting by someone without medical qualifications.[19] A study of 13,589 social media users describing their own non-approved use found fatigue, nausea, insomnia and a raised heart rate among the most often reported symptoms.[20]
- The trial results do not transfer. Every figure on this page comes from a manufactured drug, given at a set dose, raised in 4-week steps, with medical monitoring.[12] A powder of unknown purity, dosed from a seller's chart, is a different thing.
If retatrutide interests you, ask your prescriber about trials near you or about the expanded-access criteria. The FDA's own advice is to buy medicines only from state-licensed pharmacies, with a prescription.[17]
What would a stronger medication mean for eating?
Retatrutide is not available, but the eating problem it would bring is already familiar. Decreased appetite was reported as an adverse event in up to 17.1% of people on 12 mg in TRIUMPH-2, against 4.5% on placebo,[2] and 45.3% of people on 12 mg in TRIUMPH-1 saw body weight fall by 30% or more by Lilly's efficacy estimand.[12] A larger change in body weight, made on a smaller appetite, puts more weight on the quality of what does get eaten. The 2025 joint advisory on nutrition with GLP-1 therapy, written for the medications available now, sets out the priorities:[21]
- Protein first. The advisory notes that 1.2 to 1.6 g of protein per kilogram of body weight a day has been proposed for adults on these medications, to help preserve lean mass alongside strength training.[21] The numbers by body weight are in how much protein on a GLP-1, the training side is in keeping muscle on a GLP-1, and the protein calculator splits your target into small meals.
- Fluids on purpose. Normally about a fifth of the water people take in comes from food, so eating less quietly means drinking less too.[22] Vomiting and diarrhea, the commonest events in these trials, add to the loss. Daily figures are in how much water to drink on a GLP-1 and in the hydration calculator.
- Fiber and micronutrients. The advisory lists iron, calcium, magnesium, zinc and vitamins A, D, E, K, B1, B12 and C as nutrients of concern when intake falls, and suggests small, frequent, nutrient-dense meals.[21] The nutrition gap calculator shows which ones a smaller plate tends to miss, and what vitamins to take on a GLP-1 covers the evidence.
- Eat by the clock, not by hunger. The advisory suggests a reminder or alarm to eat when appetite is very low.[21] Soft, small options are in what to eat on a GLP-1 when you're not hungry.
The full map of these questions, one link each, is our GLP-1 nutrition guide.
For transparency about why this page exists on our site: we make one product, Zornava Replenish, a lemon-lime daily hydration and nutrient powder for lighter appetite days, including for people on GLP-1 medications. It is a dietary supplement, not a medication, and it has nothing to do with retatrutide. It is not on sale yet; early access opens February 9, 2027, and the early-access list is open now.
Frequently asked questions
What is GLP-3?
"GLP-3" is a nickname for retatrutide, an investigational once-weekly injection from Eli Lilly. It is not an official drug class. Retatrutide acts on three receptors, GIP, GLP-1 and glucagon, which is where the "3" comes from. Semaglutide acts on GLP-1 alone and tirzepatide on GIP and GLP-1.
Is retatrutide FDA approved?
No. As of November 13, 2026, retatrutide is not approved by the FDA or any other regulator. Lilly said on July 23, 2026 that it plans to submit it to the FDA in the first quarter of 2027. No decision date has been announced.
When will retatrutide be available?
Not before the FDA has evaluated and approved it, and the submission is planned for early 2027. Until then it is available only in Lilly's clinical trials and through a pre-approval expanded access program for adults with severe obesity and serious complications who cannot join a trial.
How does retatrutide compare with tirzepatide?
Retatrutide adds the glucagon receptor to tirzepatide's GIP and GLP-1. In separate trials, body weight fell by an average of 25.0% at 80 weeks on retatrutide 12 mg and 20.9% at 72 weeks on tirzepatide 15 mg. No head-to-head trial between the two has reported, so that is not a direct comparison.
What are the most common side effects of retatrutide?
Nausea, diarrhea, constipation and vomiting, rising with the dose. In TRIUMPH-1, nausea was reported by 42.4% on 12 mg against 14.8% on placebo. Dysesthesia, unusual skin sensations, was reported by 12.5% on 12 mg against 0.9% on placebo, and heart rate rose with the dose in phase 2.
Is it safe to buy retatrutide online for research?
No. The FDA has warned sellers of retatrutide falsely labeled "for research purposes" or "not for human consumption", and urges consumers not to buy these products, which are of unknown quality and may be harmful. Retatrutide also cannot be legally compounded.
Is retatrutide a weekly shot?
Yes, in the trials. It was given as a once-weekly injection under the skin, starting at 2 mg and raised every four weeks to the assigned dose of 4, 9 or 12 mg.
Why does nutrition matter more on a stronger GLP-1 medication?
A smaller appetite means fewer chances to get protein, fluid, fiber and micronutrients. The 2025 joint advisory for GLP-1 therapy puts protein first, suggests small, frequent, nutrient-dense meals with adequate fluids, and lists iron, calcium, vitamin D and B12 among nutrients of concern.
References
- Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. 2026;395(18):1781–1793. PubMed. PMID: 42814954. doi: 10.1056/NEJMoa2604169. TRIUMPH-1. Abstract read. Funded by Eli Lilly. ↩︎
- Eli Lilly and Company. Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. Press release (PR Newswire, via BioSpace). 2026. (topline results; regulatory plans) biospace.com. Press release of 2026-07-23. Company-reported topline results; TRIUMPH-3 not yet in a journal as of 2026-11-13. ↩︎
- Bellido V, le Roux CW, Ekinci EI, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Lancet. 2026;408(10563):1455–1472. PubMed. PMID: 42810372. doi: 10.1016/S0140-6736(26)01861-1. Abstract read. Funded by Eli Lilly; several authors are Lilly employees. ↩︎
- Novo Nordisk. Wegovy (semaglutide) injection and tablets, prescribing information and Medication Guide. DailyMed, US National Library of Medicine. 2026. DailyMed. ↩︎
- Eli Lilly and Company. Zepbound (tirzepatide) injection, prescribing information and Medication Guide. DailyMed, US National Library of Medicine. 2026. DailyMed. ↩︎
- Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389(6):514–526. PubMed. PMID: 37366315. doi: 10.1056/NEJMoa2301972. Abstract read. Funded by Eli Lilly. ↩︎
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989–1002. PubMed. PMID: 33567185. doi: 10.1056/nejmoa2032183. ↩︎
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205–216. PubMed. PMID: 35658024. doi: 10.1056/NEJMoa2206038. SURMOUNT-1. Abstract read. Funded by Eli Lilly. ↩︎
- BioPharm International. BioPharm International. 2026. biopharminternational.com. Trade-press report (2026-10-29) of Lilly’s TRANSCEND-T2D-2 topline release of 2026-10-28; figures cross-checked against PharmaShots. Company-reported results, not yet in a journal. ↩︎
- Rosenstock J, Frias J, Jastreboff AM, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Lancet. 2023;402(10401):529–544. PubMed. PMID: 37385280. doi: 10.1016/S0140-6736(23)01053-X. Abstract read. Funded by Eli Lilly. ↩︎
- Schnitzer TJ, Hunter DJ, Conaghan PG, et al. Retatrutide Once Weekly in Adults with Knee Osteoarthritis Pain and Obesity. N Engl J Med. 2026. PubMed. PMID: 43001755. doi: 10.1056/NEJMoa2610676. TRIUMPH-4 and TRIUMPH-1-OA. Published online 2026-11-08, ahead of print. Abstract read. Funded by Eli Lilly. ↩︎
- Eli Lilly and Company. Press release (PR Newswire, via BioSpace). 2026. (topline results; adverse events and discontinuations by dose) biospace.com. Press release of 2026-05-21. Company-reported topline results. ↩︎
- Grunstein RR, Somers VK, Azarbarzin A, et al. Retatrutide Once Weekly for Treatment of Obstructive Sleep Apnea. N Engl J Med. 2026. PubMed. PMID: 42904878. doi: 10.1056/NEJMoa2611477. Published online 2026-10-21, ahead of print. Abstract read. Funded by Eli Lilly. ↩︎
- Eli Lilly and Company. The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Kidney Outcomes in Adults Living With Obesity (TRIUMPH-Outcomes) (NCT06383390). ClinicalTrials.gov. 2026. clinicaltrials.gov. Registry record read via the ClinicalTrials.gov API (estimated enrollment 10,000; estimated primary completion February 2029). ↩︎
- Eli Lilly and Company. Press release. 2025. finviz.com. Press release of 2025-12-11, read as reproduced on Finviz; dysesthesia and discontinuation figures cross-checked against Patient Care (2025-12-11). Company-reported topline results. ↩︎
- Eli Lilly and Company. Pre-approval Expanded Access of Retatrutide (LY3437943) (NCT07629401). ClinicalTrials.gov. 2026. clinicaltrials.gov. Registry record read via the ClinicalTrials.gov API (status Available; last updated 2026-08-03). ↩︎
- US Food and Drug Administration. fda.gov. 2026. fda.gov. Page read (content current as of 10/01/2026). ↩︎
- Eli Lilly and Company. Lilly calls on online platforms, payment companies and regulators to shut down the illegal retatrutide black market. Press release. 2026. finviz.com. Press release of 2026-08-12, read as reproduced on Finviz (Lilly’s investor site refuses scripted requests). ↩︎
- Buzzi RM, Huber LC. Emerging risks of health optimisation: refractory nausea associated with peptide injections reported to contain retatrutide. BMJ Case Rep. 2026;19(10):e276106. PubMed. PMID: 42843917. doi: 10.1136/bcr-2026-276106. Single case report; abstract read. ↩︎
- Sehgal NKR, Tronieri JS, Rader B, Ungar L, Guntuku SC. Self-Reported Adverse Effects Among Social Media Users Taking Nonapproved Retatrutide. JAMA Netw Open. 2026;9(10):e2638929. PubMed. PMID: 42873503. doi: 10.1001/jamanetworkopen.2026.38929. Full text read (Europe PMC). Cross-sectional analysis of Reddit posts; self-reports, not verified diagnoses. ↩︎
- Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. Obesity (Silver Spring). 2025;33(8):1475–1503. (sections on low appetite, protein, fluids and nutrients of concern) Full text. PMID: 40445127. doi: 10.1002/oby.24336. ↩︎
- Institute of Medicine. Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate. National Academies Press. 2005. nap.nationalacademies.org. doi: 10.17226/10925. ↩︎
