GLP-R3What the studies show
A triple-hormone agonist in phase 3 trials. In a 48-week phase 2 study, the highest dose produced the largest weight loss ever reported for a drug.
5 min read · Large human trials · Updated November 2026
In short
- Name
- retatrutide (sold by Progression Labs as GLP-R3)
- Evidence
- Large human trials
- Bottom line
- Two randomised, placebo-controlled phase 2 trials in people, published in top journals, with phase 3 trials still in progress. That is strong evidence of effect over 36–48 weeks and no evidence yet about years.
Before you read this
This guide explains what published studies found. That is all it is.
It is not medical advice and it is not instructions for using anything. Where a dose appears, we are reporting what a named study gave the people or animals in it — a fact about the study, not an instruction to you.
The compounds here are not approved by the FDA for use in people and are sold for laboratory research only. A study tells you what happened to the subjects in it; it does not tell you what would happen to you. Talk to a doctor first.
What it is
Retatrutide is a single peptide built to act on three receptors at once: GLP-1, GIP and glucagon. GLP-1 and GIP are the gut hormones behind semaglutide and tirzepatide; adding glucagon is the new part, because glucagon receptor activation raises energy expenditure in the liver and fat tissue. It is an Eli Lilly compound, given as a once-weekly injection in its trials, and as of this writing it is an investigational drug — in phase 3 and not approved by any regulator 1.
The studies below call this molecule retatrutide. Progression Labs sells it as GLP-R3; the guide uses the store's name and the papers use theirs.
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The phase 2 obesity trial
The study everyone cites was published in the New England Journal of Medicine in 2023. It enrolled 338 adults with obesity, or overweight plus a weight-related condition, and randomised them to placebo or to retatrutide at 1, 4, 8 or 12 mg once a week for 48 weeks 1.
At 48 weeks the average change in body weight was −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 1. At the two highest doses, every participant lost at least 5% of their body weight, and at 12 mg about one in four lost 30% or more. Those are the largest average losses reported in a drug trial of this kind.
The curves had not flattened at 48 weeks, which is why the phase 3 programme runs longer. The number to keep in mind: the 8 and 12 mg groups averaged more than 20% of body weight in under a year.
Type 2 diabetes
A separate phase 2 trial, published in The Lancet the same year, tested retatrutide in 281 people with type 2 diabetes over 36 weeks against placebo and against dulaglutide, an established GLP-1 drug 2. Blood sugar, measured as HbA1c, fell by up to about two percentage points at the higher doses, and weight fell by up to about 17% — far more than dulaglutide produced 2.
Side effects in the trials
The most common side effects were the ones this class is known for: nausea, diarrhoea, vomiting and constipation, mostly mild to moderate, most frequent during dose escalation, and more common at the higher doses 1. The trials also reported a dose-related rise in resting heart rate that peaked around week 24 and eased afterwards, and some cases of abnormal skin sensations (dysaesthesia) that were not seen with the older drugs 1. Stopping because of side effects was more common on the drug than on placebo.
What is still unknown
Phase 3 is the part that answers the questions phase 2 cannot: what happens over years, in thousands of people, and to heart attacks, strokes and kidney disease rather than to a number on a scale. Lilly's TRIUMPH programme is running those trials now 3. Until they read out and a regulator reviews them, there is no approved dose, no approved use, and no safety record in the general population.
What these studies are, and aren't
Large human trials. Two randomised, placebo-controlled phase 2 trials in people, published in top journals, with phase 3 trials still in progress. That is strong evidence of effect over 36–48 weeks and no evidence yet about years.
Sources
- 1Jastreboff AM et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine, 2023.
- 2Rosenstock J 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. The Lancet, 2023.
- 3ClinicalTrials.gov. A study of retatrutide (LY3437943) in participants with obesity and cardiovascular disease (TRIUMPH-1), NCT05929066.
More in Metabolic
- 5-Amino-1MQ: What the Studies ShowA small molecule, not a peptide, that blocks the enzyme NNMT. In obese mice it trimmed weight and fat over 11 days; it has never been tested in people.
- AOD-9604: What the Studies ShowA 16-amino-acid tail of growth hormone that trimmed fat in obese mice, then failed to beat placebo in the human weight-loss trials run by its developer.
- Cagrilintide: What the Studies ShowA once-weekly amylin analogue from Novo Nordisk. Alone it produced 10.8% weight loss at 26 weeks; paired with semaglutide as CagriSema, 20.4% at 68 weeks.
- GLP-SM: What the Studies ShowThe GLP-1 agonist approved as Ozempic, Wegovy and Rybelsus: 14.9% average weight loss at 68 weeks in STEP 1, and 20% fewer major heart events in SELECT.
- GLP-TRZ: What the Studies ShowA dual GIP/GLP-1 agonist, approved as Mounjaro and Zepbound. In the 72-week SURMOUNT-1 trial, the 15 mg group lost an average of 20.9% of body weight.