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, roughly 25 to 30 percent of body weight on the top dose depending on how the trial counts people who stopped early.s2, s5
The pivotal phase 3 obesity trial (TRIUMPH-1) ran 2,339 people on 4, 9, or 12 mg against placebo. The May 2026 topline reported 17.6, 23.7, and 25.0 percent. The fuller results presented at the 2026 ADA Scientific Sessions ran higher for people who stayed on treatment, about 19, 26, and 28 percent at 80 weeks, reaching about 30 percent at 104 weeks on the top dose. The gap between the two is the difference between counting everyone and counting completers. Full peer reviewed publication is still pending.
- 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.
The phase 3 weight loss trials are done, but they were not built to answer this. The trial that is, TRIUMPH-Outcomes, is tracking heart and kidney events and is not estimated to finish until February 2029. So the honest state of things is that we now know retatrutide works and we still do not know what years of it do to you.
4.Dosing
Conservative starting protocol
Limited human dataIf a dose is working, stay on it. In the phase 3 obesity trial, 4 mg per week took off about 17.6 percent of body weight, and 4.1 percent of people quit over side effects, which is about the same share as the people on placebo. Climbing to 12 mg bought roughly 7 more points of weight loss and nearly tripled that quit rate to 11.3 percent. Most of the benefit shows up early on the ladder and most of the misery shows up at the top of it. There is no prize for climbing.
- 1
1 mg once weekly
Hold for 4 to 6 weeks
Half the dose phase 3 started people on. A gentler introduction for your gut, and the entire point of starting here.
- 2
2 mg once weekly
Hold for 4 to 6 weeks
Only if appetite control still is not where you want it after a full window at 1 mg. A bad week is not a full window.
- 3
4 mg once weekly
Hold for 4 to 6 weeks
The lowest dose phase 3 studied, and it delivered about 70 percent of the weight loss that 12 mg did while barely moving the quit rate. Plenty of people have no good reason to go past this step.
- 4
6 mg once weekly
Hold for as long as it keeps working
The ceiling for this protocol. Also a real step on the phase 3 ladder rather than a number we made up.
Ceiling: 6 mg once weekly
Trials went to 12 mg, so higher doses are studied and they do move the scale further. We stop at 6 mg anyway. Side effects climb at every step, and the trial that will tell us what retatrutide does to hearts and kidneys over years does not report until 2029, so nobody knows the long term picture yet at any dose. If 6 mg is not doing what you hoped after a real evaluation window, the answer is not 8 mg. Look at what else is going on, or talk to a clinician.s5, s6
No trial ran this ladder. Phase 3 started at 2 mg and stepped up every 4 weeks to 4, 9, or 12 mg. This protocol starts lower, moves slower, and stops earlier than that, which makes it a cautious reading of strong trial data rather than a tested regimen. That is why it is graded below the dosing data it is built on.
To turn any of these doses into a draw, use the reconstitution calculator below. Unit counts depend on your vial size and how much water you mixed it with, so there is no single number that is right for everyone. For the gear itself, see what to buy.
Educational information, not medical advice or a prescription.s2, s5
| Route(s) | subcutaneous, once weekly |
|---|---|
| Typical range | Trials have used 1 mg up to 12 mg once weekly. The phase 3 obesity trial started everyone at 2 mg and settled at 4, 9, or 12 mg. The conservative starting protocol below is lower than all of it, on purpose. |
| Frequency | Once weekly |
| Half-life | 6 days |
| Cycle guidance | Doses get raised in steps, never jumped to. Phase 3 stepped up every 4 weeks along 2, 4, 6, 9, and 12 mg so the gut had time to adjust at each level. |
| 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. |
A dose is only as good as the draw. Which syringe you need depends on how much water you mixed with, and the most common gear mistakes (a 0.5 mL syringe that cannot hold the dose, a mixing barrel that ships without needles, sizing up a needle because of body fat) are all avoidable. See what to buy: syringes, needles, and the rest of the kit.
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.
Blood level over time
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
Which do you know?
You want a set amount of compound. We show how many units to draw on the syringe.
Reminder: 1 mg = 1,000 mcg
Total amount stated on the vial, e.g. 5 mg.
How much diluent you draw into the vial.
Check this before you read the result. 1 mg = 1,000 mcg, so picking the wrong one is a 1,000x error, not a rounding error.
Result
Draw to
160 units
= 1.6 mL on a U-100 syringe
This does not fit any insulin syringe. The largest is 1 mL, which holds 100 units, and this draw is 160. Mix with about 0.56 mL of water instead so the same dose draws smaller. Do not split one dose across two draws to get around it.
- Concentration
- 2,500 mcg/mL
- Per unit
- 25 mcg / unit
- Doses per vial
- 1.3
Your settings live in the address bar, so a pasted link opens this calculator exactly as you left it.
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
- [s5]Eli Lilly and Company (2026). Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1 topline results, announced 21 May 2026). manufacturer link
- [s6]ClinicalTrials.gov (2026). The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Kidney Outcomes in Adults Living With Obesity (TRIUMPH-Outcomes), NCT06383390. Estimated completion February 2029.. regulatory link
Last reviewed 2026-07-16 · status: reviewed