Trial write-up · Phase 3 TRIUMPH programme
What the retatrutide phase 3 trials actually found
Four phase 3 trials have now reported. This is what each dose produced, what share of people reported each side effect, and how many stopped because of them — taken from Lilly's own result announcements.
Every figure below is from Eli Lilly's topline announcements of the TRIUMPH trials, or from the phase 2 trial published in the New England Journal of Medicine. Sources are listed at the bottom. Topline results are summaries released before peer review: the full papers carry detail these announcements do not.
The programme in one paragraph
Retatrutide is an investigational once-weekly injection that activates three receptors at once — GIP, GLP-1 and glucagon — which is why it gets called a triple agonist. Semaglutide hits one of those, tirzepatide two. The phase 3 programme is called TRIUMPH, and by October 2026 four of its trials had reported. It is not approved in any country, and Lilly has said it intends to file with the FDA in the first quarter of 2027.
How the dose was escalated
This is the part most write-ups get wrong, so it is worth being exact. In phase 3, everyone assigned to retatrutide started at 2 mg once weekly, and the dose was raised one step every four weeks until they reached the dose their group had been assigned. There was no 1 mg arm in phase 3 — 1 mg appeared only in the earlier phase 2 trial.
| Assigned dose | Steps on the way up | Weeks of titration |
|---|---|---|
| 4 mg | 2 mg → 4 mg | 4 |
| 9 mg | 2 mg → 4 mg → 6 mg → 9 mg | 12 |
| 12 mg | 2 mg → 4 mg → 6 mg → 9 mg → 12 mg | 16 |
Side-effect rates are published per assigned dose group across the whole trial, not per titration step. So there is no published figure for "what percentage felt sick during the four weeks at 2 mg". Anyone presenting step-by-step side-effect percentages is making them up. The numbers below are whole-trial rates for each group.
TRIUMPH-1 — obesity without diabetes
2,339 adults with obesity or overweight plus at least one weight-related condition, but without diabetes. Randomised to 4 mg, 9 mg, 12 mg or placebo for 80 weeks. Average starting weight was 112.7 kg (BMI 40.0).
| Group | Average weight change | In kg | Reached ≥25% loss | Reached ≥30% loss |
|---|---|---|---|---|
| 4 mg | −19.0% | −21.4 kg | 27.8% | 15.3% |
| 9 mg | −25.9% | −29.2 kg | 52.9% | 37.9% |
| 12 mg | −28.3% | −31.9 kg | 62.5% | 45.3% |
| Placebo | −2.2% | −2.5 kg | 2.2% | 0.5% |
A pre-specified extension kept 532 people with a starting BMI of 35 or above going to 104 weeks, moving them to their maximum tolerated dose. Those originally on 12 mg finished at −30.3% (−38.5 kg). For context, that is the range usually associated with bariatric surgery rather than with an injection.
Side effects in TRIUMPH-1
Percentage of each group reporting the event at any point in the trial.
| Event | 4 mg | 9 mg | 12 mg | Placebo |
|---|---|---|---|---|
| Nausea | 28.6% | 38.4% | 42.4% | 14.8% |
| Diarrhoea | 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% |
| Upper respiratory infection | 14.2% | 12.2% | 13.1% | 11.6% |
| Dysesthesia (odd skin sensations) | 5.1% | 12.3% | 12.5% | 0.9% |
| Urinary tract infection | 7.5% | 8.8% | 8.4% | 5.3% |
| Stopped the trial because of side effects | 4.1% | 6.9% | 11.3% | 4.9% |
Two things stand out. The gut effects climb steadily with dose — vomiting more than doubles between 4 mg and 12 mg. And at 4 mg, the share of people who quit because of side effects (4.1%) was lower than placebo (4.9%), while at 12 mg it was more than twice placebo.
TRIUMPH-2 — type 2 diabetes
1,152 adults with type 2 diabetes and obesity or overweight, randomised to 4 mg, 9 mg, 12 mg or placebo for 80 weeks. Average starting weight 106.4 kg, average HbA1c 7.7%.
| Group | Weight change | HbA1c change | Nausea | Diarrhoea | Vomiting | Stopped for side effects |
|---|---|---|---|---|---|---|
| 4 mg | −12.7% | −1.4% | 13.7% | 27.4% | 5.5% | 3.8% |
| 9 mg | −19.1% | −1.6% | 20.8% | 33.5% | 10.2% | 11.6% |
| 12 mg | −20.8% | −1.5% | 28.0% | 33.6% | 15.7% | 7.7% |
| Placebo | −4.0% | −0.2% | 8.0% | 13.2% | 4.2% | 4.9% |
Weight loss in people with diabetes was smaller than in TRIUMPH-1 — around 21% at the top dose against 28% — which is the usual pattern for this class of drug. Blood sugar control improved by much the same amount at every dose, so the extra milligrams bought weight loss rather than better HbA1c.
TRIUMPH-3 — severe obesity with heart disease
1,949 adults with a BMI of 35 or above and established cardiovascular disease, randomised to 9 mg, 12 mg or placebo for 80 weeks.
| Group | Weight change | Nausea | Diarrhoea | Decreased appetite | Stopped for side effects |
|---|---|---|---|---|---|
| 9 mg | −21.6% | 21.7% | 30.1% | 13.5% | 9.8% |
| 12 mg | −22.6% | 22.4% | 24.4% | 14.5% | 13.5% |
| Placebo | −3.2% | 5.8% | 8.7% | 3.0% | 4.8% |
At the top dose the trial also reported falls in triglycerides (37.0%), non-HDL cholesterol (16.5%), systolic blood pressure (9.3 mmHg) and hsCRP (51.2%), with waist circumference down 19.0 cm.
On heart attacks and strokes themselves, the result was not conclusive. The pre-specified analysis counted 44 major cardiovascular events on retatrutide against 52 on placebo — a hazard ratio of 0.82, with a confidence interval from 0.55 to 1.22 that crosses 1. In plain terms: the direction looks favourable, the trial was not built to prove it, and this is not the dedicated outcomes trial that would.
TRIUMPH-4 — obesity with knee osteoarthritis
405 adults with obesity or overweight and knee osteoarthritis, reported in December 2025. At 68 weeks the 12 mg group averaged −28.7% body weight against 2.1% on placebo, with knee pain scores improving substantially more than placebo. Side effects were the same gastrointestinal set.
How this compares with phase 2
The phase 2 trial ran 48 weeks in 338 adults and is where the 1 mg figure people quote comes from. At 48 weeks: −8.7% at 1 mg, −17.1% at 4 mg, −22.8% at 8 mg and −24.2% at 12 mg, against −2.1% on placebo. Side effects were again mostly gastrointestinal and dose-related, and the trial noted that starting at 2 mg rather than 4 mg reduced them — which is why phase 3 started everyone at 2 mg.
What these numbers do not tell you
- They are topline. Full peer-reviewed papers follow the announcements, and detail changes shape in review.
- "Efficacy estimand" flatters the result. It estimates what happens if people stay on treatment. The treatment-regimen estimand, which counts everyone regardless of whether they stopped, gives −25.0% rather than −28.3% at 12 mg in TRIUMPH-1. Both are real; they answer different questions.
- Trial conditions are not real life. Participants were screened, supervised, titrated slowly and supported throughout.
- Nothing here covers long-term safety. Eighty weeks is eighty weeks. The dysesthesia signal in particular is new enough to deserve attention rather than a shrug.
- It is not approved. No regulator has assessed it. Anything circulating outside a trial did not come from the manufacturer.
These trials tested a pharmaceutical-grade product, made to a known specification, given under medical supervision, with the dose raised slowly and blood work monitored. None of those conditions apply to material bought online. Nothing on this page is a protocol, a recommendation or medical advice.
If you are considering using any of this class of drug, that is a conversation to have with a doctor — including, and especially, if you would rather not have it.
Questions people ask
Why did phase 3 start at 2 mg rather than 1 mg?
Phase 2 tested both 2 mg and 4 mg as starting points and found the lower start produced fewer gastrointestinal side effects. Phase 3 took the lower start and stepped up every four weeks from there. The 1 mg arm in phase 2 was a treatment dose, not a starting step, and it produced 8.7% weight loss over 48 weeks.
Is 12 mg simply better than 9 mg?
It produced more weight loss in every trial, but the gap narrows at the top — 25.9% against 28.3% in TRIUMPH-1 — while the share of people stopping because of side effects rose from 6.9% to 11.3%. In TRIUMPH-3 the weight difference between the two doses was one percentage point.
Does it protect the heart?
Unproven. TRIUMPH-3 showed a favourable direction that did not reach statistical significance, in a trial not designed to answer the question. A dedicated cardiovascular outcomes trial, TRIUMPH-Outcomes, is running.
When might it be approved?
Lilly has indicated a US filing in the first quarter of 2027. Approval decisions take months beyond filing, and UK availability would be a separate process again.
Sources
- Eli Lilly. Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal phase 3 obesity trial (TRIUMPH-1 topline), 21 May 2026.
- Eli Lilly. Lilly's triple agonist, retatrutide, successful in two additional phase 3 obesity trials (TRIUMPH-2 and TRIUMPH-3 topline), 23 July 2026.
- Eli Lilly. TRIUMPH-4 topline announcement, 11 December 2025.
- Jastreboff AM et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine, 2023 (NEJMoa2301972).
- ClinicalTrials.gov records: NCT05929066 (TRIUMPH-1), NCT05929079 (TRIUMPH-2), NCT05882045 (TRIUMPH-3), NCT06383390 (TRIUMPH-Outcomes).