Retatrutide
Metabolic & weight lossAlso known as: LY3437943, GLP-3 (community nickname), Reta, Triple G, Triple agonist (GIP, GLP-1, glucagon)
An investigational once weekly injectable that switches on three metabolic hormone receptors at once and produced large weight loss in trials.
2.What it is / mechanism
Retatrutide is a single molecule that activates three receptors tied to metabolism at the same time: , , and . The GLP-1 and GIP actions lower appetite and improve blood sugar control, while the glucagon action nudges up energy expenditure and fat burning. A fatty acid chain lets it stick to albumin in the blood, which is what stretches its life out to once weekly dosing. Some people call it GLP-3, but that is a community nickname, not a real receptor class.s1, s2
3.What the evidence supports
- Strong human dataProduces large weight loss in adults with obesity, up to about 24 percent of body weight at 48 weeks.s2
From a randomized, placebo controlled phase 2 trial. Weight was still dropping when the study ended. Phase 3 trials (the TRIUMPH program) are still running.
- Limited human dataImproves blood sugar in people with type 2 diabetes.s3
Supported by phase 2 data pooled in a meta analysis. Not yet confirmed by completed phase 3 trials.
- Limited human dataReduces liver fat in fatty liver disease.s4
From a phase 2a trial. Early but promising.
No completed phase 3 trial and no long term human safety record exist yet.
4.Dosing
| Route(s) | subcutaneous, once weekly |
|---|---|
| Typical range | Trials used 1 mg up to 12 mg once weekly. Most people start at 1 mg or 2 mg. |
| Frequency | Once weekly |
| Half-life | 6 days |
| Cycle guidance | Doses are usually raised in steps every 4 weeks, for example 1 mg, then 2, 4, 8, and 12 mg, so the gut has time to adjust. |
| Notes | With a around 6 days, retatrutide builds up over the first month of steady dosing before it levels off at a plateau. This is why gut side effects often ease a few weeks into a given dose, and why raising the dose too quickly tends to bring them back. Try the plotter below to see the buildup. |
Saturation plotter
Adjust the protocol to see how Retatrutide builds up in the blood over a cycle and whether it reaches a steady-state plateau.
Retatrutide: Blood level over time
Relative level (mg)Steady-state avg
4.9 mg
Peak / trough
7.2 / 3.2
Time to ~90% saturation
2.8 wk
Saturation at cycle end
100%
Teaching model that assumes even dose spacing, instant absorption, and single compartment clearance. An educational estimate, not a clinical PK simulation or dosing advice.
5.Reconstitution
| Vial sizes | 5 mg, 10 mg, 15 mg |
|---|---|
| Diluent | Bacteriostatic water for multi dose vials, or sterile water for single use |
| Concentration | Example: a 10 mg vial plus 1 mL of water gives 10 mg/mL, so 4 mg is 0.4 mL, which is 40 units on a U-100 syringe. Adjust the water volume to land on an easy unit count. |
| Notes | A finished retatrutide product is expected to arrive as a prefilled pen. Research material is sold as lyophilized (freeze dried) vials, commonly 5 mg to 15 mg. |
Reconstitution calculator
Pick your vial size and how much water you add to see the draw volume and syringe units for a dose. Open the full calculator →
Inputs
Reminder: 1 mg = 1,000 mcg
Total amount stated on the vial, e.g. 5 mg.
How much diluent you draw into the vial.
Target dose per injection, in mcg. 1 mg = 1,000 mcg.
Result
Draw to
160 units
= 1.6 mL on your syringe
- Concentration
- 2,500 mcg/mL
- Per unit
- 25 mcg / unit
- Doses per vial
- 1.3
Educational estimate only. Not medical or dosing advice. Verify every calculation independently before use.
6.Storage & stability
Lyophilized (dry)
| Temp | Freeze for long term storage, or 2 to 8 short term |
|---|---|
| Shelf life | Many months when frozen |
| Notes | Keep dry and out of light until you mix it. |
Reconstituted
| Temp | 2 to 8 (refrigerated) |
|---|---|
| Shelf life | About 4 weeks |
| Notes | Do not freeze after mixing. Discard if the solution turns cloudy. |
7.Reported side effects
- SeriousAcute pancreatitis(rare)s2One serious case in the phase 2 obesity trial, along with symptomless rises in pancreatic enzymes. Seek care for severe, lasting abdominal pain.
- CautionNausea(common)s2The most common effect. It tends to spike in the days after each dose increase, then settle.
- CautionVomiting or diarrhea(common)s2
- CautionConstipation(common)s2
- CautionFaster heart rate(common)s2A known effect across this drug class.
- CautionTingling or altered skin sensation(uncommon)s2Reported as mild to moderate in trials, and it did not cause people to stop.
- InfoReduced appetite(common)s2Expected, and part of how the drug works.
8.Interactions & stacking risks
Raises the risk of low blood sugar. These medicines may need to be lowered under medical supervision.
Retatrutide slows stomach emptying, which can change how quickly swallowed drugs are absorbed.
- WarningOther GLP-1 or incretin drugs (semaglutide, tirzepatide)
Stacking with another incretin agonist is not studied and raises the chance of severe gut effects.
9.Contraindications / who should avoid
- SeriousPersonal or family history of medullary thyroid cancer, or MEN2
Drugs in this class caused thyroid C cell tumors in rodents. No human cases have shown up in trials, but the precaution stands.
- SeriousPregnancy or breastfeeding
No safety data, and rapid weight loss is not advised during pregnancy.
- WarningHistory of pancreatitis
A possible pancreatitis signal means extra caution is warranted.
10.COA & purity notes
| Common adulterants | underdosed or mislabeled vials, retatrutide sold as a blend with other GLP-1 drugs, endotoxin or contaminants from non sterile production |
|---|---|
| Mislabeling | Because there is no approved retatrutide product yet, all research material is unregulated. Actual content can differ from the label, so a recent third party COA matters. |
| Notes | Not FDA approved. The quality of research material is not overseen by any regulator. |
11.Sources
- [s1]The Lancet (2022). LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b multiple ascending dose trial. rct link
- [s2]New England Journal of Medicine (2023). Triple Hormone Receptor Agonist Retatrutide for Obesity, a Phase 2 Trial. rct link
- [s3]PMC (peer reviewed meta analysis) (2025). Efficacy and safety of retatrutide for obesity: a systematic review and meta analysis of randomized controlled trials. review link
- [s4]Nature Medicine (2024). Triple hormone receptor agonist retatrutide for metabolic dysfunction associated steatotic liver disease: a randomized phase 2a trial. rct link
Last reviewed 2026-07-07 · status: reviewed