Retatrutide is a peptide that stimulates three hormone receptors at once: GLP-1, GIP and the glucagon receptor. In the phase 3 TRIUMPH-1 trial it reduced body weight by an average of 25.0% over 80 weeks at the highest dose, and by 28.3% in the analysis that assumes full adherence. It is not approved for sale in any country and remains an investigational molecule.
That sets it apart from semaglutide and tirzepatide, which are registered medicines. The mechanism of incretins and a comparison of all three molecules are covered in the pillar article on GLP-1 and in the separate comparison.
What is triple agonism?
Retatrutide targets three receptors: GLP-1, GIP and glucagon. The first two are incretin pathways, shared with tirzepatide. The third, glucagon, is what distinguishes retatrutide from the rest of the group.
Incretin pathways act mainly on satiety and on glucose-dependent insulin secretion. The glucagon receptor is tied to processes in the liver and to energy expenditure rather than to appetite itself. A review published in 2026 in Expert Review of Clinical Pharmacology reports that in people with metabolic dysfunction-associated steatotic liver disease, liver fat content fell by up to 86% with retatrutide. How much the glucagon pathway contributes to the final effect on weight has not yet been broken down into numbers.
What did the TRIUMPH-1 trial show?
TRIUMPH-1 is a phase 3 trial with 2,339 people with obesity without diabetes, run under the number NCT05929066. The main observation period lasted 80 weeks, and 532 participants entered an extension to 104 weeks. Three doses were tested: 4 mg, 9 mg and 12 mg weekly, against placebo.
After 80 weeks the average weight reduction was 17.6% at 4 mg, 23.7% at 9 mg and 25.0% at 12 mg. In the placebo group it was 3.9%. A reduction of at least 30% of body weight was reached by 15.3% of people at 4 mg, 37.9% at 9 mg and 45.3% at 12 mg. In the extension to 104 weeks, in the subgroup with a baseline body mass index of 35 or above, the average reduction reached 30.3%, about 85 pounds.
Why do different sources quote different numbers?
Two sets of results circulate for the same trial, and both are true. What separates them is the method of counting, called an estimand in the protocol.
The treatment-regimen estimand counts every participant regardless of whether they finished and whether they turned to other weight management methods. That is where 17.6%, 23.7% and 25.0% against 3.9% on placebo come from. The efficacy estimand estimates the effect assuming the participant takes the drug as directed. That method gives 19.0%, 25.9% and 28.3% against 2.2% on placebo.
The first number says what to expect in the real world, interruptions and deviations included. The second says how much the molecule itself delivers in someone who stays on it. Comparing a result from one trial counted one way with a result from another trial counted the other way leads to false conclusions.
What did TRIUMPH-2 and TRIUMPH-3 show?
Results for both were announced on 23 July 2026. TRIUMPH-2 covered adults with obesity or overweight and type 2 diabetes. Average weight reduction after 80 weeks was 12.7% at 4 mg, 19.1% at 9 mg and 20.8% at 12 mg. Glycated haemoglobin fell from a baseline of 7.7% by 1.4 points at 4 mg, 1.6 points at 9 mg and 1.5 points at 12 mg, against 0.2 points on placebo.
TRIUMPH-3 covered adults with severe obesity and established cardiovascular disease, with or without type 2 diabetes. Average weight reduction there reached 22.6% over 80 weeks. Results in groups with diabetes are lower than in groups without it, and that pattern repeats across the incretin class.
What side effects were recorded?
They were more frequent than with the other two molecules in the group and concerned the digestive tract. At the highest dose, 42.4% of participants reported nausea against 14.8% on placebo, 32.0% diarrhoea against 13.5%, and 25.3% vomiting against 4.8%. Constipation was reported by 26.1% of people on the highest dose.
The share of people who stopped treatment because of side effects rose with the dose: 4.1% at 4 mg, 6.9% at 9 mg and 11.3% at 12 mg, against 4.9% on placebo. That rise matters when reading the results, because the highest dose delivers both the largest weight reduction and the most discontinuations.
Is retatrutide available as a medicine?
It is not. As of the publication of this article, retatrutide remains in phase 3 clinical trials and holds no registration as a medicine in the European Union or the United States. The manufacturer has announced plans to file for approval in the United States in the first quarter of 2027. Registration in the European Union requires a separate procedure on its own timeline.
In our shop it appears only as research material: retatrutide. It is not sold for human use, and a “research” label gives no guarantee of the quality expected of a registered medicine. The cart and the checkout are in English and prices are shown in Polish zloty. Purchase rules are set out on the legal warning page.
Frequently asked questions
Which receptors does retatrutide act on?
Three: the GLP-1 receptor, the GIP receptor and the glucagon receptor. It shares the first two with tirzepatide; the third is what sets it apart.
How much weight did retatrutide reduce in trials?
In TRIUMPH-1, an average of 25.0% over 80 weeks at the 12 mg dose, against 3.9% on placebo. In the analysis assuming full adherence it was 28.3%, and in the extension to 104 weeks, in the subgroup with a body mass index of 35 or above, 30.3%.
Why do some sources say 25% and others 28%?
Both numbers come from the same trial and differ in the method of counting. 25.0% is the treatment-regimen estimand, covering all participants regardless of interruptions, and 28.3% is the efficacy estimand, the effect under full adherence.
What are the side effects of retatrutide?
Gastrointestinal symptoms dominate. At the highest dose, 42.4% of participants reported nausea, 32.0% diarrhoea, 26.1% constipation and 25.3% vomiting. Treatment was stopped because of side effects by 11.3% of people on the highest dose.
Does retatrutide work in type 2 diabetes?
In TRIUMPH-2, which covered people with type 2 diabetes, glycated haemoglobin fell by 1.4 to 1.6 percentage points from a baseline of 7.7%, against 0.2 points on placebo. It is not, however, an approved treatment for diabetes.
Can retatrutide be bought as a medicine?
It cannot. Retatrutide is not a registered medicine in any country and remains in phase 3 trials.
Where this information comes from
The TRIUMPH-1 figures under the treatment-regimen estimand, that is 17.6%, 23.7%, 25.0% and 3.9% on placebo, come from a report by The Pharmaceutical Journal in May 2026. The figures under the efficacy estimand, that is 19.0%, 25.9%, 28.3% and 2.2% on placebo, together with the 2,339 participants, the trial number NCT05929066, the 532-person extension, the shares reaching at least 30% reduction, the 30.3% result at 104 weeks and the side effect and discontinuation rates, come from an Eli Lilly press release published on PR Newswire.
The TRIUMPH-2 and TRIUMPH-3 results, including weight reductions, changes in glycated haemoglobin and the plan to file for approval in the first quarter of 2027, come from a release by the same company dated 23 July 2026. The figure for liver fat falling by up to 86% comes from a review by Panou and co-authors in Expert Review of Clinical Pharmacology, 2026, PMID 41785010, read through Europe PMC. All pages were checked on 7 September 2026.