Retatrutide is an experimental weight-loss and diabetes drug made by Eli Lilly, code name LY3437943. It is a single peptide molecule that activates three hormone receptors at once: GIP, GLP-1 and glucagon. That is why people call it a “triple agonist” or “triple G”. Semaglutide (Ozempic, Wegovy) hits one of those receptors, and tirzepatide (Mounjaro, Zepbound) hits two.
The results so far are well beyond the flagship trials of semaglutide and tirzepatide. In the 80-week phase 3 TRIUMPH-1 trial, people in the highest dose arm lost an average of 28.3% of their body weight, versus 2.2% on placebo. The side effects are mostly the familiar stomach ones, plus a new skin-sensation signal called dysesthesia.
Retatrutide is not approved anywhere, including Canada. Lilly says it plans to submit it for U.S. approval in Q1 2027. Until then, it is only available to people enrolled in clinical trials.
Retatrutide in one minute
If you have only heard the word in a TikTok or a news headline, here is the basic fact sheet.
| Question | Answer |
|---|---|
| What is it? | An investigational peptide drug for obesity, type 2 diabetes and related conditions |
| Who makes it? | Eli Lilly and Company (the maker of Mounjaro and Zepbound) |
| Code name | LY3437943 |
| Drug type | Triple hormone receptor agonist: GIP, GLP-1 and glucagon |
| How often (in trials) | Once weekly; the molecule’s half-life is about 6 days |
| Best weight-loss result | 28.3% average at 80 weeks (TRIUMPH-1, highest dose arm); 30.3% in a 104-week extension |
| Approved? | No, not in any country |
| U.S. filing | Planned for Q1 2027, per Lilly |
| Canada | Not authorized by Health Canada |
The rest of this guide explains each line in plain English, and links out to deeper TrueLabs posts where a topic needs its own page.
How retatrutide works: the three receptors
Your gut and pancreas release hormones after you eat. These hormones tell your brain you are full, tell your pancreas to release insulin, and tell your liver what to do with fuel. Retatrutide is a lab-designed peptide that imitates three of those signals at once.
1. GLP-1 (glucagon-like peptide-1)
This is the receptor that made semaglutide famous. Activating it reduces appetite, helps the pancreas release insulin when blood sugar is high, and slows how fast food leaves the stomach.
2. GIP (glucose-dependent insulinotropic polypeptide)
GIP is the second gut hormone that tirzepatide added to the mix. It also supports insulin release after meals and appears to add to the appetite and weight effects of GLP-1. Lilly’s discovery paper reports that, in lab tests, retatrutide has more activity at the GIP receptor than at the other two.
3. Glucagon
This is the new piece. Glucagon is usually thought of as insulin’s opposite, the hormone that raises blood sugar between meals. That makes it a surprising thing to put in a diabetes drug. The bet is that, combined with GLP-1 and GIP, glucagon’s other effects add to weight loss and liver-fat reduction without wrecking blood sugar control. The next section explains why.
The key point: retatrutide is one molecule, not a blend of three drugs. In the 2022 discovery paper (Coskun et al., Cell Metabolism), Lilly scientists described it as having “balanced GCGR and GLP-1R activity but more GIPR activity” in lab testing. GCGR is the glucagon receptor.
Why glucagon matters
If GLP-1 and GIP already produce 20% weight loss with tirzepatide, why add glucagon? Two reasons stand out in the research.
Energy expenditure
GLP-1 and GIP mainly work on the “calories in” side: you eat less. Glucagon appears to act on the “calories out” side. In Lilly’s discovery work in mice, the authors reported that weight loss “was augmented by the addition of GCGR-mediated increases in energy expenditure,” on top of the reduced food intake driven by GIP and GLP-1.
A caveat: that finding comes from mice. Whether retatrutide meaningfully raises energy expenditure in humans, and by how much, has not been settled in the data released so far.
Liver fat
Glucagon acts directly on the liver, which is where retatrutide’s most striking early result came from. In a phase 2 sub-study of people with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD, formerly called fatty liver disease), presented at the AASLD Liver Meeting in 2023:
- Liver fat fell by an average of 81.7% (8 mg arm) and 86.0% (12 mg arm) at 48 weeks, versus a 4.6% increase on placebo.
- 89% and 93% of those arms reached normal liver fat levels (under 5%), versus 0% on placebo.
That is why Lilly is running a phase 3 program in MASLD as well as obesity. If you are interested in the condition itself, our guide to fatty liver treatment in Canada covers the approved options.
What about blood sugar?
The worry with glucagon is obvious: it raises blood sugar. In practice, the GLP-1 and GIP effects appear to outweigh it. In TRIUMPH-2, people with type 2 diabetes saw their A1C fall by 1.4 to 1.6 percentage points from a starting 7.7%, versus 0.2 on placebo. In TRANSCEND-T2D-1, A1C fell by up to 2.0 points, and about 90% of people on retatrutide reached an A1C below 7%.
Timeline: from lab to phase 3
Retatrutide moved fast by drug-development standards. Here is the path, with each step verified against the published paper or Lilly announcement.
| When | Milestone |
|---|---|
| 2022 | Lilly publishes the discovery and first human data for LY3437943 in Cell Metabolism. A single dose produced weight loss that persisted up to day 43. |
| 2022 | Phase 1b trial in type 2 diabetes published in The Lancet. Placebo-adjusted weight loss reached up to 8.96 kg in 12 weeks; half-life about 6 days. |
| June 2023 | Phase 2 obesity trial published in the New England Journal of Medicine: 24.2% average weight loss at 48 weeks in the 12 mg arm. A parallel phase 2 type 2 diabetes trial is published in The Lancet. |
| November 2023 | Liver-fat sub-study presented at AASLD: up to 86% reduction in liver fat at 48 weeks. |
| 2023 | The phase 3 TRIUMPH program begins. Lilly says it eventually enrolled more than 5,800 participants. |
| December 11, 2025 | First phase 3 readout, TRIUMPH-4 (obesity plus knee osteoarthritis): 28.7% average weight loss at 68 weeks in the 12 mg arm, plus large reductions in knee pain. |
| May 21, 2026 | TRIUMPH-1, the pivotal obesity trial: 28.3% at 80 weeks (12 mg), and 30.3% in a 104-week extension. |
| June 2026 | Full TRIUMPH-1 data and the first diabetes phase 3 (TRANSCEND-T2D-1) presented at the American Diabetes Association Scientific Sessions. |
| July 23, 2026 | TRIUMPH-2 (obesity plus type 2 diabetes) and TRIUMPH-3 (obesity plus heart disease) read out positive. Lilly says it now has the data package for global submissions. |
| Q1 2027 (planned) | U.S. submission for approval, after Lilly completes its manufacturing (CMC) package. |
Still running: TRIUMPH-OUTCOMES (NCT06383390), a roughly five-year trial testing whether retatrutide reduces heart events and kidney decline, and phase 3 studies in chronic low back pain and MASLD.
Headline results
Here are the main phase 3 weight-loss results, using Lilly’s primary efficacy figures. Doses are the fixed target doses tested in each trial, reported as trial facts.
| Trial | Who was in it | Length | Average weight loss (retatrutide arms) | Placebo |
|---|---|---|---|---|
| TRIUMPH-1 | 2,339 adults with obesity or overweight, no diabetes | 80 wk | 19.0% (4 mg) / 25.9% (9 mg) / 28.3% (12 mg) | 2.2% |
| TRIUMPH-4 | 445 adults with obesity and knee osteoarthritis | 68 wk | 26.4% (9 mg) / 28.7% (12 mg) | 2.1% |
| TRIUMPH-2 | 1,152 adults with obesity and type 2 diabetes | 80 wk | 12.7% / 19.1% / 20.8% | 4.0% |
| TRIUMPH-3 | 1,949 adults with BMI 35+ and established heart disease | 80 wk | 21.6% (9 mg) / 22.6% (12 mg) | 3.2% |
Some highlights behind those averages:
- A quarter to a third of body weight. In TRIUMPH-1’s 12 mg arm, 62.5% of people lost at least 25% of their body weight, and 45.3% lost at least 30%.
- Knee pain. In TRIUMPH-4, knee pain scores (WOMAC) fell by about 75% on retatrutide versus about 40% on placebo.
- Heart risk factors. In TRIUMPH-3, the 12 mg arm saw triglycerides fall 37.0%, systolic blood pressure fall 9.3 mmHg, and hsCRP (an inflammation marker) fall 51.2%.
- Heart events: not settled. TRIUMPH-3’s cardiovascular event analyses were inconclusive. Confidence intervals crossed 1 for both MACE-5 and MACE-3. That is what TRIUMPH-OUTCOMES is for.
Two notes on reading these numbers. Weight loss was lower in TRIUMPH-2, which enrolled people with type 2 diabetes. And the “efficacy estimand” figures Lilly leads with assume people stayed on treatment. Figures that count everyone, including those who stopped, are lower. In TRIUMPH-4, for example, the 12 mg result was 23.7% on that basis. For a full trial-by-trial breakdown, see Retatrutide phase 3 results.
What conditions is retatrutide being studied for?
Weight loss gets the headlines, but Lilly’s program is broader. Based on Lilly’s July 2026 announcement, retatrutide is in phase 3 testing for:
- Obesity and overweight with weight-related health problems (TRIUMPH-1, TRIUMPH-3).
- Type 2 diabetes, both with obesity (TRIUMPH-2) and for blood sugar control (TRANSCEND-T2D-1).
- Knee osteoarthritis pain (TRIUMPH-4). Our knee pain treatment guide covers today’s approved options.
- Obstructive sleep apnea in people with obesity (a TRIUMPH-1 basket trial).
- Chronic low back pain, MASLD (fatty liver), and cardiovascular and kidney outcomes (TRIUMPH-OUTCOMES).
Lilly says its first submissions will cover obesity, knee osteoarthritis pain and obstructive sleep apnea. The other uses depend on trials that are still running.
Retatrutide vs semaglutide vs tirzepatide
This is the short version. Our full guide, Retatrutide vs tirzepatide vs semaglutide, goes deeper. If you just want the Ozempic angle, see Retatrutide vs Ozempic.
| Semaglutide | Tirzepatide | Retatrutide | |
|---|---|---|---|
| Brand names | Ozempic, Wegovy | Mounjaro, Zepbound | None yet |
| Maker | Novo Nordisk | Eli Lilly | Eli Lilly |
| Receptors | GLP-1 | GIP + GLP-1 | GIP + GLP-1 + glucagon |
| Flagship obesity trial | STEP 1 (68 wk) | SURMOUNT-1 (72 wk) | TRIUMPH-1 (80 wk) |
| Average weight loss, top dose | 14.9% | 20.9% | 28.3% |
| Nausea, top dose | 44.2% | 31.0% | 42.4% |
| Stopped due to side effects, top dose | 7.0% | 6.2% | 11.3% |
| Status | Approved medicine | Approved medicine | Investigational |
These are separate trials with different lengths, populations and analysis methods, so treat the comparison as approximate. No head-to-head trial of retatrutide against either drug has reported results.
The simple summary: each new receptor has added weight loss. Retatrutide’s side-effect profile looks broadly similar to the other two, not dramatically better or worse. The one new item is the dysesthesia signal.
Side effects in brief
We cover this symptom by symptom, with every trial’s numbers, in Retatrutide side effects. The essentials:
- Stomach effects are the most common: nausea, diarrhea, constipation and vomiting. In TRIUMPH-1, nausea ranged from 28.6% to 42.4% across dose arms, versus 14.8% on placebo.
- Dysesthesia (tingling or unusual skin sensitivity) was reported in up to 20.9% of one phase 3 arm (TRIUMPH-4, 12 mg), versus 0.7% on placebo in that trial. It was generally mild.
- Heart rate rose in phase 2, peaking around 24 weeks and then declining.
- Stopping due to side effects ranged from about 2% to 18% across phase 3 arms, versus 0% to 5% on placebo.
- Lean mass: a phase 2 body-composition sub-study concluded that weight loss did not come at the cost of disproportionate lean-mass loss. See muscle loss on GLP-1 drugs for context.
For the bigger-picture safety question, see Is retatrutide safe?.
Approval status and expected FDA filing
As of October 2026, retatrutide is not approved by any regulator. That includes the U.S. FDA, Health Canada and the European Medicines Agency. Lilly has said the drug is available only to clinical trial participants until regulatory review is complete.
The key dates:
- July 23, 2026: after TRIUMPH-2 and TRIUMPH-3, Lilly said it has “the clinical data package to support global submissions” for obesity, knee osteoarthritis pain and obstructive sleep apnea.
- Q1 2027: Lilly says it is completing the chemistry, manufacturing and controls (CMC) package needed for a U.S. Biologics License Application, and “plans to subsequently submit retatrutide in Q1 2027 for U.S. approval.”
- After that: the FDA review itself. A U.S. approval decision can only come after the filing, so retatrutide cannot realistically reach pharmacies before then. Lilly has not given an approval date.
Filings in other countries, including Canada, have not been dated publicly by Lilly. We track the latest in Is retatrutide approved?.
Retatrutide in Canada
Here is the plain answer for Canadians: retatrutide is not an authorized drug in Canada. It has no Drug Identification Number (DIN), and it is not available by regular prescription.
Health Canada has been explicit about products sold online. Its April 9, 2026 advisory names retatrutide among unauthorized injectable peptide drugs that Canadians should not buy or use. It says these products have not been assessed for safety, efficacy or quality. It also states that labelling such as “For Research Use Only – Not for Human Consumption” does not make them legal or exempt them from regulatory requirements. Health Canada says it is working with the Canada Border Services Agency to stop unauthorized shipments.
What that means in practice:
- Anything sold as “retatrutide” in Canada today is not Lilly’s trial product and is not an approved medicine.
- Research-grade compounds are for laboratory research, not for people. The trial results on this page describe Lilly’s pharmaceutical product under medical supervision, not anything bought online.
- If you want help with weight today, approved GLP-1 medicines with a DIN are available through your doctor or nurse practitioner and a licensed pharmacy. Our weight-loss injections in Canada guide covers those options.
For the full Canadian picture, including what to watch for when a Canadian submission happens, read Retatrutide in Canada.
Nicknames: Reta, GLP-3, RT3
Retatrutide has picked up several informal names online. Quickly:
- Reta: simple shorthand, common on Reddit and social media.
- “GLP-3”: a popular nickname meaning “the third-generation GLP drug” or “three receptors”. It is not a scientific name. There is no hormone called GLP-3, and the third receptor retatrutide targets is glucagon.
- RT3: the catalogue name some research suppliers, including TrueLabs, use for research-grade retatrutide.
- LY3437943: Lilly’s official development code, used in the early papers.
We unpack where each name came from in Retatrutide, GLP-3 and other names.
Retatrutide myths
“Myth: Retatrutide is already approved somewhere.”
No country has approved it. Lilly’s U.S. submission is planned for Q1 2027, and the drug remains limited to clinical trial participants.
“Myth: GLP-3 is a new hormone.”
There is no GLP-3. The nickname is shorthand for a drug that hits three receptors: GLP-1, GIP and glucagon.
“Myth: Glucagon makes it bad for diabetes.”
The trials say otherwise. A1C fell by 1.4 to 1.6 points in TRIUMPH-2, and about 90% of retatrutide participants reached an A1C under 7% in TRANSCEND-T2D-1.
“Myth: It’s proven to protect your heart.”
Not yet. Blood pressure, triglycerides and inflammation markers improved, but TRIUMPH-3’s cardiovascular event results were inconclusive. The dedicated outcomes trial is still running.
“Myth: Most of the weight lost is muscle.”
Some lean mass is lost with any major weight loss. But the phase 2 body-composition sub-study found large fat-mass reductions and concluded the weight loss did not come at the cost of disproportionate lean-mass loss. Phase 3 body-composition data are still to come.
“Myth: Online ‘research’ retatrutide is the same as the trial drug.”
The trial results apply to Lilly’s manufactured product given under medical supervision. Health Canada says unauthorized peptide products have not been assessed for safety, efficacy or quality, and that research-use labelling does not change their legal status.
For researchers
TrueLabs supplies RT3 (Retatrutide) from $90 for in vitro and laboratory research only. It is not for human or veterinary use, and nothing in this article describes how to use it. Labs studying incretin receptor pharmacology may also compare TZ-2 (Tirzepatide) from $73 and Cagrilintide from $40. Before any experiment, check identity and purity against the certificate of analysis. Our guides How to read a peptide COA and the COA library show what to look for.
FAQ
Tap a question to reveal the answer.
What is retatrutide in simple terms?
Retatrutide is an experimental once-weekly drug from Eli Lilly that activates three hormone receptors involved in appetite, blood sugar and metabolism: GIP, GLP-1 and glucagon. It is being developed for obesity, type 2 diabetes and related conditions. It is not yet approved anywhere.
Who makes retatrutide?
Eli Lilly and Company, the same company that makes tirzepatide (Mounjaro and Zepbound). Its development code is LY3437943. Lilly published the discovery work in 2022 and began the phase 3 TRIUMPH program in 2023.
How much weight do people lose on retatrutide?
In the 80-week TRIUMPH-1 trial, average weight loss was 19.0%, 25.9% and 28.3% in the 4, 9 and 12 mg arms, versus 2.2% on placebo. In a 104-week extension of people with a BMI of 35 or more, the highest figure was 30.3%. People with type 2 diabetes lost less, around 13% to 21% in TRIUMPH-2.
Why does retatrutide include glucagon?
In Lilly’s animal research, adding glucagon-receptor activity increased energy expenditure on top of the appetite effects of GLP-1 and GIP. Glucagon also acts on the liver. In a phase 2 sub-study, liver fat fell by up to 86% at 48 weeks.
Is retatrutide better than Ozempic or Mounjaro?
For weight loss, its trial results are larger: 28.3% in TRIUMPH-1 versus 14.9% for semaglutide in STEP 1 and 20.9% for tirzepatide in SURMOUNT-1. These were separate trials, though, and no head-to-head result has been published. Side effects look broadly similar, and unlike the other two, retatrutide is not an approved medicine.
When will retatrutide be approved?
Nobody knows the exact date. Lilly plans to submit retatrutide for U.S. approval in Q1 2027, and an FDA decision would follow that review. Lilly has not announced dates for Canada or other countries.
Is retatrutide available in Canada?
Not as an approved medicine. Retatrutide has no DIN, and it can only be used legitimately within a clinical trial. Health Canada’s April 2026 advisory names it among unauthorized peptide drugs and says research-use labelling does not make such products legal.
Is retatrutide the same as GLP-3?
“GLP-3” is an informal nickname for retatrutide, not a scientific term. There is no hormone called GLP-3. The name refers loosely to the drug hitting three receptors: GLP-1, GIP and glucagon.
What are the main side effects of retatrutide?
The most common are nausea, diarrhea, constipation and vomiting, mostly mild to moderate and most frequent while doses were being increased. Trials also reported dysesthesia (unusual skin sensations) and a temporary heart-rate increase in phase 2. Between about 2% and 18% of people in phase 3 arms stopped because of side effects.
Is retatrutide a peptide?
Yes. Retatrutide is a single synthetic peptide engineered to act on three receptors at once. It is not a blend of three separate drugs.
Related reading
- Retatrutide Side Effects: Every Symptom, With Trial Rates
- Retatrutide Phase 3 Results
- Is Retatrutide Approved?
- Retatrutide in Canada
- Retatrutide vs Tirzepatide vs Semaglutide
- The Next Weight-Loss Drugs After Ozempic
References
- Coskun T, Urva S, Roell WC, et al. 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 Metab. 2022;34(9):1234-1247. PubMed
- Urva S, Coskun T, Loh MT, et al. 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. Lancet. 2022;400(10366):1869-1881. PubMed
- Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023. doi:10.1056/NEJMoa2301972. PubMed
- 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. doi:10.1016/S0140-6736(23)01053-X. PubMed
- Patient Care Online. Novel “triagonist” retatrutide resolved steatosis in over 85% of patients with MASLD and obesity (AASLD Liver Meeting 2023, Sanyal AJ et al.). November 10, 2023. Patient Care
- Eli Lilly and Company. Press release on topline TRIUMPH-4 results for retatrutide in obesity and knee osteoarthritis. December 11, 2025. Lilly
- Eli Lilly and Company. Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1). Press release, May 21, 2026. Lilly
- HCPLive. Retatrutide meets weight loss endpoints in phase 3 obesity trial (TRIUMPH-1). May 21, 2026. HCPLive
- HCPLive. TRANSCEND-T2D-1: Retatrutide demonstrates superior weight loss and A1c results versus placebo. June 6, 2026. HCPLive
- Eli Lilly and Company. Lilly’s triple agonist retatrutide successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C (TRIUMPH-2, TRIUMPH-3). Press release, July 23, 2026. BioSpace
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021. doi:10.1056/NEJMoa2032183. PubMed
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387(3). doi:10.1056/NEJMoa2206038. PubMed
- The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Kidney Outcomes in Adults Living With Obesity (TRIUMPH-OUTCOMES). NCT06383390. ClinicalTrials.gov
- Health Canada. Think twice before injecting peptides bought online: unauthorized products can seriously harm your health. Advisory RA-81874, April 9, 2026. Health Canada
This article summarizes published research and regulatory information for information only and is not medical advice. TrueLabs research compounds are sold for in vitro and laboratory research use only and are not intended for human or veterinary use.