Retatrutide’s phase 2 result, an average 24.2% weight loss after 48 weeks on the highest dose, made it the most closely watched molecule in obesity research. Phase 3 had harder questions to answer: would the effect hold in thousands of people, in people with diabetes or heart disease, over longer periods, and at what cost in side effects? By the autumn of 2026, all four core TRIUMPH trials had reported.
This guide walks through each trial, the safety signals that matter, how to read the headline numbers, and what happens next. Doses are described as lowest, middle and highest rather than in milligrams.
The short answer
- TRIUMPH-1 (2,339 adults with obesity or overweight, 80 weeks): the highest dose produced an average 28.3% weight loss, and 45.3% of those participants lost at least 30%. The lowest dose produced 19.0%.
- TRIUMPH-4 (obesity with knee osteoarthritis, 68 weeks): 28.7% on the highest dose, with improvements in knee pain.
- In harder-to-treat groups, results were smaller but still large: 20.8% in people with type 2 diabetes (TRIUMPH-2) and up to 22.6% in people with established cardiovascular disease (TRIUMPH-3).
- Side effects were mostly gastrointestinal, plus a newer signal, dysesthesia (abnormal skin sensations). In TRIUMPH-1, 11.3% stopped the highest dose because of adverse events, compared with 4.9% on placebo.
- Retatrutide is not approved anywhere. Lilly says it now has the data to support regulatory submissions worldwide.
From phase 2 to TRIUMPH
Retatrutide activates three receptors at once: GIP, GLP-1 and glucagon. In the 2023 phase 2 trial published in the New England Journal of Medicine, adults with obesity lost an average of 24.2% of their body weight after 48 weeks on the highest dose. The phase 3 TRIUMPH programme was designed to test that result in larger, longer and more varied populations. Our GLP-1 research map shows how retatrutide compares with single and dual agonists, and our GIP explainer covers the receptor it shares with tirzepatide.
TRIUMPH-1: the main obesity trial
TRIUMPH-1 enrolled 2,339 adults with obesity or overweight and followed them for 80 weeks. In topline results announced in May 2026, participants on the highest dose lost an average of 28.3% of their body weight, and 45.3% of them lost at least 30%, a degree of weight loss Lilly noted is usually associated with bariatric surgery. The lowest dose, reached with a single escalation step, produced 19.0%, with a lower rate of stopping for adverse events than placebo. Detailed results were presented at the American Diabetes Association’s Scientific Sessions in June 2026.
TRIUMPH-4: obesity and knee osteoarthritis
Reported in December 2025, TRIUMPH-4 enrolled adults with obesity and knee osteoarthritis. Over 68 weeks, the highest dose produced an average 28.7% weight loss, together with improvements in knee pain. It was also the trial in which dysesthesia stood out most: as reported, about one in five participants on the highest dose experienced it, and 18.2% stopped that dose because of adverse events, compared with 4.0% on placebo.
TRIUMPH-2: obesity and type 2 diabetes
People with type 2 diabetes usually lose less weight on incretin drugs, and TRIUMPH-2 followed that pattern: 20.8% on the highest dose at 80 weeks. Blood sugar improved substantially. A1C fell by up to 1.6 percentage points from an average starting level of 7.7%, compared with 0.2 points on placebo, and up to 40% of participants reached an A1C in the normal range. More than half no longer met the body-mass-index definition of obesity.
TRIUMPH-3: obesity and cardiovascular disease
TRIUMPH-3 enrolled people with severe obesity and established cardiovascular disease, with or without diabetes, and tested the middle and highest doses. Weight loss reached up to 22.6% at 80 weeks.
The trial also counted major cardiovascular events, but there were too few to conclude anything. In a pre-specified analysis there were 44 five-component events on retatrutide versus 52 on placebo (hazard ratio 0.82, 95% confidence interval 0.55 to 1.22) and 27 versus 23 three-component events (hazard ratio 1.12, 0.64 to 1.96). Neither difference was statistically significant; answering that question needs a trial designed and powered for cardiovascular outcomes.
The safety picture
The most common adverse events were gastrointestinal: nausea, diarrhea, constipation, vomiting and decreased appetite, generally mild to moderate and most frequent while doses were being increased. Two other findings deserve attention.
Dysesthesia, meaning abnormal skin sensations such as tingling, burning or heightened sensitivity, occurred far more often on retatrutide than on placebo. Lilly reported the events as generally mild to moderate, most resolved during treatment, and most participants who had them stayed in the trial. Skin-sensitivity events had already appeared in phase 2. Their cause is not established.
Discontinuation for adverse events rose with dose in most trials, and was highest in the older, sicker populations.
| Trial | Dysesthesia: retatrutide vs placebo | Stopped for adverse events: retatrutide vs placebo |
|---|---|---|
| TRIUMPH-1 | 5.1%, 12.3%, 12.5% vs 0.9% | 4.1%, 6.9%, 11.3% vs 4.9% |
| TRIUMPH-2 | 4.5%, 5.6%, 7.3% vs 0.7% | 3.8%, 11.6%, 7.7% vs 4.9% |
| TRIUMPH-3 (two doses) | 6.4%, 6.4% vs about 1.3% | 9.8%, 13.5% vs 4.8% |
| TRIUMPH-4 (two doses) | About 8.8%, 20.9% vs 0.7% | About 12.2%, 18.2% vs 4.0% |
Figures are listed from lowest to highest dose tested in each trial. TRIUMPH-1 and TRIUMPH-2 figures come from Lilly’s announcements; the TRIUMPH-3 placebo dysesthesia rate and the TRIUMPH-4 figures are as reported in published summaries of those announcements.
Research-grade retatrutide for laboratory work, with a batch-matched COA.
View retatrutideHow to read these numbers
- Two ways of counting. Obesity trials report an “efficacy” figure for participants who stayed on treatment and a “treatment-regimen” figure for everyone randomized. In TRIUMPH-1 the highest dose produced 28.3% on the first measure and 25.0% on the second. Both are honest; they answer different questions.
- Different populations. People with diabetes or heart disease typically lose less weight, so TRIUMPH-2 and TRIUMPH-3 aren’t directly comparable with TRIUMPH-1.
- Averages hide spread. Some participants lose far more than the average and some far less.
- Announcements first, papers later. Topline figures come from company releases; full peer-reviewed papers add detail and occasionally revise numbers.
- No head-to-head results yet. None of these trials compared retatrutide directly with another drug.
For a deeper primer on study quality, see how to read a peptide study.
What happens next
In July 2026, Lilly said that with TRIUMPH-2 and TRIUMPH-3 complete it had the clinical data to support global regulatory submissions for obesity, knee osteoarthritis pain and obstructive sleep apnea, and that it planned to file with the US FDA in the first quarter of 2027. Approval decisions rest with regulators, and timelines are not guaranteed. Retatrutide is not approved anywhere.
Our retatrutide guide covers the molecule itself.
Reasonably well established
- Large, dose-related weight loss across four phase 3 trials.
- Meaningful A1C improvement in people with type 2 diabetes.
- Gastrointestinal effects as the most common adverse events.
Open questions
- The cause and long-term significance of dysesthesia.
- Effects on heart attacks, strokes and deaths.
- How weight and safety outcomes look beyond two years.
RetatrutideGIP, GLP-1 and glucagon triple agonistView product and COA
SurvodutideGLP-1 and glucagon dual agonistView product and COA
CagrilintideLong-acting amylin analogueView product and COA
Research use only. Retatrutide from Pure Peptides Canada is a laboratory reagent for in-vitro research. It is not an approved drug or the investigational product used in clinical trials, it is not for human or veterinary use, and nothing in this article is dosing or medical guidance.
Frequently asked questions
What did the retatrutide phase 3 trials show?
Across four TRIUMPH trials, retatrutide produced large, dose-related weight loss: about 28% on the highest dose in people with obesity, and 20.8% to 22.6% in people with type 2 diabetes or cardiovascular disease. Side effects were mostly gastrointestinal, with dysesthesia emerging as a notable signal.
How much weight did participants lose in TRIUMPH-1?
Participants on the highest dose lost an average of 28.3% of their body weight over 80 weeks among those who stayed on treatment, or 25.0% counting everyone randomized. 45.3% lost at least 30%.
What is dysesthesia, and why does it matter for retatrutide?
Dysesthesia means abnormal skin sensations such as tingling, burning or heightened sensitivity. In TRIUMPH-1 it affected 5.1% to 12.5% of participants on retatrutide versus 0.9% on placebo. Most events were mild to moderate and resolved, but the cause is not yet understood.
How many participants stopped retatrutide because of side effects?
In TRIUMPH-1, 4.1%, 6.9% and 11.3% stopped on the lowest, middle and highest doses because of adverse events, compared with 4.9% on placebo. Rates were higher in the trials of older and sicker populations.
Did retatrutide reduce heart attacks or strokes?
That isn’t known yet. TRIUMPH-3 counted cardiovascular events, but there were too few to draw conclusions, and neither the five-component nor the three-component comparison was statistically significant.
When will retatrutide be approved?
It isn’t approved anywhere yet. In July 2026 Lilly said it had the data to support global regulatory submissions, but decisions and timelines rest with regulators.
Is retatrutide available in Canada?
It is not an authorized drug in Canada. Health Canada’s April 2026 advisory listed retatrutide among unauthorized injectable peptides it had seized. Research-grade retatrutide is a laboratory reagent and is not for human use.
Follow the incretin research
Our research library tracks GLP-1, GIP and glucagon compounds as trial results arrive, with research-grade reagents and batch-matched COAs for laboratory work.
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(6):514–526.
- Eli Lilly and Company. Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. May 21, 2026. Lilly
- Eli Lilly and Company. Lilly’s triple agonist, retatrutide, successful in two additional Phase 3 obesity trials. July 2026. Lilly
- Eli Lilly and Company. Retatrutide delivered substantial weight loss and A1C reduction in people with obesity and type 2 diabetes (TRIUMPH-2). September 29, 2026. Lilly
- Health Canada. Think twice before injecting peptides bought online. April 2026. Recalls and safety alerts
- Jensen K. Lilly, with new data, to seek FDA approval of obesity drug retatrutide. BioPharma Dive. July 23, 2026. BioPharma Dive
- Health Canada. New drug submissions under review (list current to August 31, 2026). Government of Canada
For laboratory research use only. Not for human or veterinary use. This article summarizes published and announced clinical research for educational purposes and is not medical advice. Nothing here is intended to diagnose, treat, cure or prevent any disease.