Retatrutide
GLP-1 + GIP + Glucagon triple receptor agonist (Eli Lilly LY3437943)
Retatrutide is an investigational once-weekly injectable that activates three hormone receptors: GLP-1, GIP and glucagon. It is in phase 3 trials for obesity and related conditions and is not FDA-approved. In its phase 2 trial, adults on 12 mg weekly lost an average of 24.2% of body weight over 48 weeks.
Quick reference
How Retatrutide is dosed in practice
There is no approved retatrutide dose. In the phase 2 obesity trial (NEJM 2023), participants took 1, 4, 8 or 12 mg once a week for 48 weeks. Most arms started at 2 mg (some at 4 mg; one arm stayed at 1 mg throughout) and were stepped up to their target dose.
Starting at 2 mg rather than 4 mg partly reduced the digestive side effects in that trial.
Where the numbers come from: these are trial doses, not a prescription. Retatrutide is legally available only inside clinical trials; products sold online as 'research' retatrutide are unregulated and their content is unknown. If it is approved, the label will set the doses.
Work out the units to draw with the reconstitution calculator and how long a vial lasts with the vial duration calculator.
How Retatrutide works
Retatrutide activates three receptors. The GLP-1 and GIP parts work as in tirzepatide: less appetite, slower stomach emptying, better insulin response. The glucagon part is thought to increase energy expenditure and fat breakdown in the liver — how much it adds in people is still being worked out.
In its phase 2 trial, retatrutide 12 mg produced a mean body-weight change of -24.2% at 48 weeks. In SURMOUNT-1, tirzepatide 15 mg produced -20.9% at 72 weeks. These were separate trials, not a head-to-head comparison; the phase 3 TRIUMPH trials will give longer data.
In a substudy of the phase 2 trial, liver fat fell substantially at the higher doses. Phase 3 trials are testing whether this translates into benefits for fatty liver disease.
Critical practical note: retatrutide is not FDA-approved and is legally available only in clinical trials. Long-term safety is unknown, and the phase 3 trials may identify risks not yet seen.
Safety + side-effect profile
Digestive side effects were the most common in the phase 2 trial; they were dose-related, mostly mild to moderate, and partly reduced when the starting dose was 2 mg rather than 4 mg.
Seen in phase 2: dose-dependent increases in heart rate that peaked at 24 weeks and declined afterwards. No label yet: until there is one, the warnings for approved GLP-1 drugs are a reasonable guide — including avoiding use with a personal or family history of medullary thyroid carcinoma (MTC) or MEN 2, and not using it in pregnancy.
Interactions: never combine with semaglutide, tirzepatide or liraglutide — overlapping action, untested combination. With insulin or sulfonylureas, low blood sugar is a risk.
Lean mass: as with other weight-loss drugs, part of the weight lost can be lean tissue; resistance training and enough protein are the standard advice.
- • Nausea, diarrhea, vomiting or constipation (dose-related, mostly during dose increases)
- • Higher resting heart rate (peaked at 24 weeks in phase 2)
- • Reduced appetite (intended effect)
- • Reflux / heartburn (especially with large meals)
- • Less 'food noise' (intended effect)
Frequently asked
What is Retatrutide?
Retatrutide (Eli Lilly LY3437943) is an investigational once-weekly injectable that activates GLP-1, GIP and glucagon receptors. It is in phase 3 trials (the TRIUMPH program) and is not FDA-approved. In phase 2, adults on 12 mg weekly lost an average of 24.2% of body weight over 48 weeks.
Retatrutide vs Tirzepatide — which is more effective?
In its phase 2 trial, retatrutide 12 mg produced a mean body-weight change of -24.2% at 48 weeks; in SURMOUNT-1, tirzepatide 15 mg produced -20.9% at 72 weeks. The two have not been compared head to head, so which is more effective is not yet known. In both programs gastrointestinal side effects were the most common, and doses were raised in steps. Tirzepatide is FDA-approved; retatrutide is not.
What is the typical Retatrutide titration?
There is no approved dose. In the phase 2 trial, participants took 1, 4, 8 or 12 mg once weekly for 48 weeks; most arms started at 2 mg (some at 4 mg; one arm stayed at 1 mg) and were stepped up to the target dose. Starting at 2 mg partly reduced digestive side effects. These are trial doses, not a prescription.
Should I switch from Tirzepatide to Retatrutide?
Not outside a clinical trial. Retatrutide isn't FDA-approved, so it's legally available only in studies, while tirzepatide is approved with years of data. If your weight loss has plateaued, talk to your prescriber about approved options or trial enrollment, and never combine the two.
Does Retatrutide help with NAFLD / fatty liver?
Possibly. In a substudy of the phase 2 trial, liver fat fell substantially at the higher doses. Phase 3 trials are testing whether this leads to clinical benefits in fatty liver disease; retatrutide is not approved for any use yet.
What are the long-term safety concerns?
Unknown. The phase 2 trial lasted 48 weeks: digestive side effects were the most common, and heart rate rose in a dose-dependent way, peaking at 24 weeks and declining afterwards. The phase 3 TRIUMPH trials will provide longer safety data.
Is Retatrutide research-chemical only right now?
Retatrutide is not FDA-approved; legally, it's available only inside clinical trials. Products sold online as 'research chemicals' are unregulated — their identity, dose and purity are unknown, and they aren't made for human use. Tirzepatide and semaglutide are approved alternatives.
Are there side effects beyond GLP-1 standard ones?
In phase 2, the main signal beyond the usual GLP-1 effects was a dose-dependent rise in heart rate that peaked at 24 weeks and then declined. Digestive side effects were the most common and were dose-related.
Related compounds
Often researched, stacked, or compared with Retatrutide.
Cited research
Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med, 2023.
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 conducted in the USA. Lancet, 2023.
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