Retatrutide, Eli Lilly’s “triple agonist,” has now posted five positive phase 3 trials. The headline: in TRIUMPH-1, adults with obesity lost an average of 28.3% of body weight at 80 weeks on the top dose, and 30.3% at 104 weeks in an extension, the largest average weight loss ever reported for an obesity drug. In people with type 2 diabetes the losses were smaller (up to 20.8%), as is typical for this class. In TRIUMPH-4, it also cut knee arthritis pain substantially.
The trade-offs are real: more nausea and vomiting than older drugs at the highest dose, more people stopping because of side effects, and a new signal of dysesthesia (odd skin sensations) that wasn’t prominent with semaglutide or tirzepatide. Lilly plans to file with the FDA in the first quarter of 2027; Canada typically follows. Below, every trial, every number that matters, and how to read them.
What retatrutide is
Retatrutide (development code LY3437943) is a single molecule that activates three hormone receptors at once:
| Receptor | Natural hormone | Main effect |
|---|---|---|
| GLP-1 | Glucagon-like peptide-1 | Fullness, slower stomach emptying, insulin release |
| GIP | Glucose-dependent insulinotropic polypeptide | Insulin release, fat tissue effects, may reduce nausea |
| Glucagon | Glucagon | Raises energy expenditure, burns liver fat |
Semaglutide (Ozempic, Wegovy) hits only GLP-1. Tirzepatide (Mounjaro, Zepbound) hits GLP-1 and GIP. Retatrutide adds glucagon, which is the key difference. Glucagon is usually thought of as the hormone that raises blood sugar, but it also increases calorie burning and pulls fat out of the liver. Combined with GLP-1’s appetite effects and GIP’s metabolic effects, the idea is more weight loss from both eating less and burning more. It is given as a once-weekly injection in trials.
For a deeper comparison of the three molecules, see retatrutide vs tirzepatide vs semaglutide.
The TRIUMPH program at a glance
| Trial | Population | Length | Top-dose weight loss | Placebo |
|---|---|---|---|---|
| TRIUMPH-4 (Dec 2025) | Obesity + knee osteoarthritis (n=445) | 68 weeks | 28.7% | 2.1% |
| TRIUMPH-1 (May 2026) | Obesity or overweight, no diabetes (n=2,339) | 80 weeks | 28.3% | Not reported in summary |
| TRIUMPH-1 extension | BMI 35+ subgroup | 104 weeks | 30.3% | — |
| TRIUMPH-2 (July 2026) | Type 2 diabetes + obesity (n=1,152) | 80 weeks | 20.8% | 4.0% |
| TRIUMPH-3 (July 2026) | Severe obesity + heart disease (n=1,949) | 80 weeks | 22.6% | 3.2% |
Doses studied were 4 mg, 9 mg and 12 mg once weekly (TRIUMPH-4 tested 9 and 12 mg). These are trial doses reported from published results, not guidance; retatrutide is not approved for use anywhere.
TRIUMPH-1: the headline trial
TRIUMPH-1 was the largest and most important trial: 2,339 adults with obesity, or overweight plus at least one weight-related condition, and without diabetes, randomized to retatrutide or placebo for 80 weeks.
| Dose | Average weight loss at 80 weeks | Approximate pounds |
|---|---|---|
| 4 mg | 19.0% | 47 lb |
| 9 mg | 25.9% | 64 lb |
| 12 mg | 28.3% | 70 lb |
Even the lowest dose produced weight loss comparable to tirzepatide’s best results in SURMOUNT-1. The two higher doses put average losses in a range that, until recently, only bariatric surgery reached.
Detailed results were presented at the American Diabetes Association’s Scientific Sessions in June 2026. As always, averages hide a spread: some participants lost far more, and some much less.
The two-year extension: 30.3%
A subgroup of 532 participants with a baseline BMI of 35 or higher continued blinded treatment to 104 weeks. On the 12 mg dose, average weight loss reached 30.3% (about 85 lb). Two things stand out:
- Weight loss was still slowly increasing between 80 and 104 weeks, rather than plateauing early, a pattern different from semaglutide, which usually plateaus around 60 weeks.
- The extension enrolled people with higher starting BMI, who tend to lose more in absolute terms, so the figure is not directly comparable to the 80-week main result.
TRIUMPH-2: type 2 diabetes
People with type 2 diabetes consistently lose less weight on incretin drugs than people without diabetes. TRIUMPH-2 enrolled 1,152 adults with type 2 diabetes and obesity or overweight:
| Dose | Weight loss at 80 weeks |
|---|---|
| 4 mg | 12.7% |
| 9 mg | 19.1% |
| 12 mg | 20.8% |
| Placebo | 4.0% |
Blood sugar control improved markedly: HbA1c fell by up to 1.6 percentage points from a baseline of 7.7%, versus 0.2 points on placebo. Discontinuation due to side effects ranged from 3.8% to 11.6% across doses, versus 4.9% on placebo.
TRIUMPH-3: severe obesity and heart disease
TRIUMPH-3 tested retatrutide in a higher-risk group: 1,949 adults with severe obesity (BMI 35+) and established cardiovascular disease, with or without diabetes. Weight loss reached 21.6% on 9 mg and 22.6% on 12 mg, versus 3.2% on placebo, over 80 weeks.
This trial matters for safety: it shows the drug can be given to people with existing heart disease. But it is not a cardiovascular outcomes trial; it was not designed to show fewer heart attacks or strokes. That kind of evidence (which semaglutide has from the SELECT trial) will take longer.
TRIUMPH-4: knee arthritis
TRIUMPH-4 was actually the first phase 3 trial to report, in December 2025. It enrolled 445 adults with obesity (average BMI over 40) and knee osteoarthritis:
- Weight loss at 68 weeks: 26.4% (9 mg) and 28.7% (12 mg), versus 2.1% on placebo.
- Knee pain (WOMAC pain score): fell by 4.5 and 4.4 points on retatrutide versus 2.4 on placebo.
- Discontinuation due to side effects: 12.2% and 18.2% versus 4% on placebo, notably higher than in other trials.
It follows semaglutide’s STEP 9 trial in showing that large weight loss eases arthritis pain. For all knee options, see our knee pain treatment guide.
Where it started: the phase 2 results
The 2023 phase 2 trial in the New England Journal of Medicine first put retatrutide on the map: up to 24.2% average weight loss at 48 weeks in adults with obesity, a result that had never been seen with a drug at that point (Jastreboff et al., 2023). Phase 2 also flagged a dose-dependent rise in heart rate that peaked around six months and then declined, something researchers have watched closely in phase 3.
How to read the numbers (estimands)
Obesity trials often report two versions of the same result, which confuses headlines:
- Efficacy estimand: what happens in people who keep taking the drug as intended. Higher numbers; this is what most press releases lead with.
- Treatment-regimen (or treatment-policy) estimand: includes everyone randomized, including those who stopped. Lower numbers, closer to real-world use.
When comparing drugs, compare like with like. Many of the figures above are efficacy-estimand numbers from company and conference summaries; full publications will add the more conservative estimates.
Side effects across the trials
Retatrutide’s side effects look like the rest of the class, mostly gastrointestinal, but more frequent at the highest dose. From TRIUMPH-1:
| Side effect | 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% |
| Stopped due to side effects | 4.1% | 6.9% | 11.3% | 4.9% |
Key takeaways:
- GI effects are dose-dependent and mostly occur during dose increases, easing over time.
- The 4 mg dose had a discontinuation rate similar to placebo while still producing about 19% weight loss, which may make it an attractive option for many people if approved.
- The 12 mg dose roughly doubles the dropout rate. In TRIUMPH-4, dropout on 12 mg reached 18.2%.
- Other reported events included upper respiratory and urinary tract infections.
For a full safety discussion, see is retatrutide safe?
The dysesthesia signal
The most novel safety finding is dysesthesia: unusual skin sensations such as tingling, burning, prickling or heightened sensitivity to touch. In TRIUMPH-4 it occurred in 8.8% (9 mg) and 20.9% (12 mg) of participants, versus 0.7% on placebo. TRIUMPH-1 also reported mild-to-moderate dysesthesia.
- Most cases were described as mild and did not lead to stopping treatment.
- The mechanism is unclear. It hasn’t been a prominent feature of semaglutide or tirzepatide, so it may relate to glucagon receptor activity or to the speed and scale of weight loss.
- Regulators will look closely at how long it lasts and whether it resolves after stopping.
How it compares to Zepbound and Wegovy
| Semaglutide (Wegovy) | Tirzepatide (Zepbound) | Retatrutide | |
|---|---|---|---|
| Receptors | GLP-1 | GLP-1 + GIP | GLP-1 + GIP + glucagon |
| Main obesity trial | STEP 1: ~15% at 68 weeks | SURMOUNT-1: ~21% at 72 weeks | TRIUMPH-1: 28.3% at 80 weeks |
| Cardiovascular outcomes data | Yes (SELECT) | Ongoing | Not yet |
| Status in Canada | Approved; generic semaglutide since 2026 | Approved | Not approved |
Head-to-head trials are the only fair comparison, and none comparing retatrutide directly with tirzepatide has reported yet. Cross-trial comparisons are rough because populations and durations differ. For the approved options available today, see weight loss injections in Canada.
Liver fat and metabolic results
The glucagon component makes retatrutide especially interesting for fatty liver disease. In a phase 2 substudy of people with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), the 8 mg and 12 mg doses cut liver fat by more than 80%, and 86% to 93% of participants reached normal liver fat levels by 24 to 48 weeks (Sanyal et al., 2024). We cover this in our fatty liver treatment guide.
Across trials, retatrutide also lowered blood pressure, triglycerides and markers of inflammation, consistent with the large weight loss.
What we still don’t know
- Hard outcomes: whether it reduces heart attacks, strokes and deaths.
- Long-term safety beyond two years, including the dysesthesia signal and heart rate effects.
- Muscle and bone: how much of the weight lost is lean mass at these unprecedented levels (see muscle loss on GLP-1 drugs).
- What happens after stopping: weight regain is expected, as with other drugs in the class.
- Head-to-head performance against tirzepatide.
- Price and coverage.
Approval timeline: US and Canada
| Milestone | Timing |
|---|---|
| Phase 2 published | 2023 |
| First phase 3 (TRIUMPH-4) | December 2025 |
| TRIUMPH-1 | May 2026 |
| TRIUMPH-2 and 3 | July 2026 |
| Planned FDA submission | First quarter of 2027 |
| Realistic US decision | Late 2027 to 2028, based on typical review times |
| Canada | Usually follows the US; no Health Canada submission listed as of late 2026 |
We track this in is retatrutide approved? (updated as news breaks).
The grey market problem
The phase 3 headlines have driven huge demand for “retatrutide” sold online years before approval. What’s sold that way is not the medicine studied in TRIUMPH: it is an unregulated research chemical, and its identity, purity and dose depend entirely on the supplier. Independent testing of grey-market peptides has found underdosed and impure products. Health Canada warned in April 2026 against injecting peptides bought online.
TrueLabs supplies retatrutide (from $90) strictly as a research compound for laboratory use, with independent HPLC and mass-spectrometry reports in our COA library. It is not a medicine and is not for human use. If your goal is weight loss, the approved options, including much cheaper generic semaglutide, are the safe route today.
| Related research compound | Receptor targets | From |
|---|---|---|
| Retatrutide | GLP-1, GIP, glucagon | $90 |
| Tirzepatide | GLP-1, GIP | $73 |
| Cagrilintide | Amylin | $40 |
Retatrutide myths: what it can’t promise
The size of retatrutide’s results has produced a wave of overstated claims online. Here is what the data do not show:
- “Everyone loses 30%.” The 30.3% figure is an average from a two-year extension in people with a BMI of 35 or more, on the top dose, in those who stayed on treatment. Individual results varied widely, and some participants lost far less.
- “It’s a cure for obesity.” Like other drugs in the class, it treats obesity while it’s taken. Weight regain after stopping is expected based on everything known about incretin drugs.
- “It has fewer side effects because it’s newer.” At the top dose it caused more nausea, vomiting and dropouts than placebo, and introduced a dysesthesia signal.
- “It protects your heart.” TRIUMPH-3 showed weight loss in people with heart disease, but no trial has yet shown fewer heart attacks or strokes.
- “It’s basically approved.” Approval requires regulatory review of the full data package. Filing is planned for early 2027, and regulators can ask for more information or restrict use.
- “Online retatrutide is the same thing.” Grey-market vials are unregulated research chemicals with no guarantee of identity, purity or dose.
- “Higher dose is always better.” The 4 mg dose produced about 19% weight loss with dropout similar to placebo; the 12 mg dose added weight loss but nearly tripled side-effect dropouts.
Who was in the trials
Trial results apply best to people similar to those enrolled. Across the program:
- Adults only; no children or adolescents.
- Starting weight was high: in TRIUMPH-4, average BMI was over 40 and average weight about 113 kg.
- Specific conditions were studied separately: no diabetes (TRIUMPH-1), type 2 diabetes (TRIUMPH-2), established heart disease (TRIUMPH-3), knee osteoarthritis (TRIUMPH-4).
- Common exclusions in obesity trials include pregnancy, certain thyroid cancers, history of pancreatitis, recent major cardiovascular events and uncontrolled medical conditions.
- Lifestyle counselling was provided to all participants, including those on placebo, which partly explains placebo weight loss.
That means results may differ for people with lower starting BMI, older adults with frailty, or groups under-represented in the trials.
Blood pressure, heart rate and lipids
| Measure | What the trials have shown |
|---|---|
| Blood pressure | Lowered, consistent with the amount of weight lost |
| Triglycerides | Reduced |
| Heart rate | A dose-dependent increase in phase 2, peaking around six months and then easing; monitored closely in phase 3 |
| Blood sugar / HbA1c | Large reductions in type 2 diabetes (up to 1.6 points in TRIUMPH-2) |
| Liver fat | Normalized in most participants on higher doses in a phase 2 substudy |
Heart rate increases are a known feature of GLP-1-based drugs, usually a few beats per minute. Because glucagon can also raise heart rate, regulators will look carefully at this in the full data.
Glossary of trial terms
| Term | Meaning |
|---|---|
| Phase 3 | Large trials designed to confirm benefit and safety before approval |
| Randomized, double-blind, placebo-controlled | Participants are randomly assigned, and neither they nor investigators know who gets the drug |
| Topline results | The first headline numbers released by the company, before full publication |
| Efficacy estimand | Results if everyone took the drug as intended |
| Treatment-regimen estimand | Results including people who stopped; closer to real-world use |
| Discontinuation due to adverse events | The share of participants who stopped because of side effects |
| Extension | Continued treatment beyond the main trial period in a subgroup |
| Cardiovascular outcomes trial | A trial designed to show fewer heart attacks, strokes or deaths |
| WOMAC | A standard questionnaire scoring knee and hip arthritis pain and function |
| BLA / NDA | The formal application for FDA approval |
How to follow the news yourself
- ClinicalTrials.gov: search “retatrutide” to see every registered trial, its status and design.
- Peer-reviewed journals: full results usually appear in journals like the New England Journal of Medicine or The Lancet after conference presentations.
- Company investor releases: Eli Lilly announces topline results and filing plans.
- Health Canada: the Drug Product Database lists approved products; a public list of submissions under review shows new drugs being evaluated.
- Our tracker: is retatrutide approved? is updated when regulatory news breaks.
What people search: hair loss, gallbladder, muscle and more
Does retatrutide cause hair loss?
Hair shedding is a known effect of rapid, large weight loss with any method, and it has been reported with semaglutide (about 3%) and tirzepatide (about 5.7%) in trials. Given that retatrutide produces even larger losses, some degree of telogen effluvium is expected in a subset of people. Full rates will be clearer in complete publications. See hair loss on GLP-1 drugs.
Does retatrutide affect the gallbladder?
Gallstones and gallbladder inflammation are more common with rapid weight loss of any kind and are a recognized class effect of GLP-1-based drugs. Regulators will review gallbladder events across the TRIUMPH program; anyone with right upper abdominal pain, fever or yellowing of the skin on these drugs needs medical assessment.
Does retatrutide cause muscle loss?
Any large weight loss includes some lean mass. The proportion with retatrutide hasn’t been fully reported for phase 3. Strength training and adequate protein are the main protective measures; see muscle loss on GLP-1 drugs.
Does retatrutide lower blood sugar in people without diabetes?
It improves insulin sensitivity and glucose levels, but GLP-1-based drugs rarely cause low blood sugar on their own because their insulin effect depends on glucose being elevated. The risk of hypoglycemia rises when combined with insulin or sulfonylureas.
Can retatrutide be used in pregnancy?
No. Weight-loss drugs in this class are not used in pregnancy, and trials excluded pregnant participants.
Does retatrutide work for people who didn’t respond to semaglutide?
That specific question hasn’t been answered by a dedicated trial yet. Because it adds GIP and glucagon pathways, it’s plausible that some people respond differently, but this needs data.
What a head-to-head with tirzepatide would need to show
Tirzepatide already beat semaglutide directly in the SURMOUNT-5 trial. For retatrutide to be judged clearly superior, a head-to-head trial would ideally show:
- Greater weight loss at doses with similar tolerability, not just at a top dose with higher dropout.
- Comparable or better safety, including heart rate, dysesthesia and GI effects.
- Body composition data, showing whether extra weight loss is mostly fat.
- Outcome benefits over time, such as cardiovascular, kidney or liver outcomes.
Until then, the best comparison is cautious cross-trial reading, which favours retatrutide on average weight loss and tirzepatide on maturity of evidence and availability.
FAQ
Tap a question to reveal the answer.
How much weight did people lose on retatrutide in phase 3?
In TRIUMPH-1, adults without diabetes lost an average of 19.0%, 25.9% and 28.3% of body weight at 80 weeks on the 4, 9 and 12 mg doses. In a 104-week extension, the 12 mg group reached 30.3%.
Is retatrutide better than Zepbound?
Its trial results show larger average weight loss than tirzepatide’s, but no head-to-head trial has reported, and cross-trial comparisons are imperfect. It also has higher side-effect dropout at the top dose.
What are retatrutide’s main side effects?
Nausea, diarrhea, constipation and vomiting, which are dose-dependent. Dysesthesia, unusual skin sensations, is a newer signal seen especially at the highest dose.
What is dysesthesia on retatrutide?
Abnormal skin sensations such as tingling, burning or sensitivity. In TRIUMPH-4 it affected 20.9% on 12 mg versus 0.7% on placebo; most cases were mild and didn’t lead to stopping.
When will retatrutide be approved?
Lilly plans to file with the FDA in the first quarter of 2027. A US decision is realistic in late 2027 to 2028, and Canada usually follows the US.
Is retatrutide available in Canada?
Not as a medicine. It is not approved by Health Canada and cannot be prescribed. Products sold online are unregulated research chemicals.
Does retatrutide help with type 2 diabetes?
In TRIUMPH-2, people with type 2 diabetes lost up to 20.8% of body weight and their HbA1c fell by up to 1.6 percentage points.
Does retatrutide reduce liver fat?
Yes. In a phase 2 substudy, 86% to 93% of participants on higher doses reached normal liver fat by 24 to 48 weeks.
Who should not take retatrutide?
It is not approved, so it should not be taken outside clinical trials. Trials typically excluded pregnancy, a history of pancreatitis, certain thyroid cancers and recent major cardiovascular events.
Does retatrutide cause hair loss?
Hair shedding is common with rapid, large weight loss and has been reported with semaglutide and tirzepatide. Some shedding is expected with retatrutide too; complete rates will come with full publications.
Related reading
- The next weight loss drugs after Ozempic
- Is retatrutide approved?
- Is retatrutide safe?
- Hair loss on GLP-1 drugs
References
- Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med. 2023;389:514–526. PubMed
- AJMC. Retatrutide achieves up to 30.3% average weight loss in phase 3 TRIUMPH-1 trial. May 2026. AJMC
- PharmExec. Retatrutide delivers up to 22.6% weight loss in two new phase III trials. July 2026. PharmExec
- Healio. Retatrutide confers up to 28.7% weight loss, reduction in knee osteoarthritis pain (TRIUMPH-4). January 2026. Healio
- Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024;30:2037–2048. PubMed
- Ground News. Eli Lilly says it will file for approval of next-generation obesity drug in 2027. July 2026. Ground News
This article summarizes published and company-reported trial results for information only; it is not medical advice. Doses mentioned are those tested in clinical trials. TrueLabs research compounds are sold for in vitro and laboratory research use only and are not intended for human or veterinary use.