Retatrutide dosage & reconstitution guide
Retatrutide is the triple-receptor agonist producing the largest weight-loss numbers seen in an obesity trial so far — and it is still investigational. Here is what the published dosing actually was, how the reconstitution maths works, and how it compares to tirzepatide and semaglutide.
Retatrutide has no marketing authorisation anywhere. Every figure on this page comes from published clinical trials run with medical supervision, screening and monitoring. This is educational reference material so you can understand the research — not a protocol to self-administer.
What retatrutide is
Retatrutide (LY3437943) is a single peptide that activates three receptors at once: GLP-1, GIP and glucagon. GLP-1 and GIP suppress appetite and slow gastric emptying; the glucagon arm is the novel part, increasing hepatic energy expenditure and fat oxidation. That third lever is why the Phase 2 results outran the dual agonists.
It is also why the side-effect picture differs. Glucagon-receptor agonism can push fasting glucose and heart rate up, which is manageable in a monitored trial and much less so unsupervised.
Retatrutide dosage in the Phase 2 trials
The obesity trial randomised participants to 1, 4, 8 or 12 mg weekly subcutaneous injections, all reached by slow escalation. Mean weight reduction at 48 weeks was about 24% in the 12 mg arm. The escalation pattern below reflects the published schedule.
| Step | Weekly dose | Notes |
|---|---|---|
| Weeks 1–4 | 1–2 mg weekly | Starting step; most nausea shows up here |
| Weeks 5–8 | 2–4 mg weekly | Only if the prior step was tolerated |
| Weeks 9–16 | 4–8 mg weekly | Escalation held or reversed on GI symptoms |
| Week 17+ | 8–12 mg weekly | Highest trial arms; largest side-effect burden |
The single most important detail is the pace, not the ceiling. Gastrointestinal tolerability tracks how fast you escalate. Trial protocols held or stepped back down whenever nausea or vomiting appeared, and there was no benefit to rushing.
Reconstitution maths
Lyophilised vials need bacteriostatic water before anything can be measured. The whole calculation is one division: concentration (mg/mL) = vial strength (mg) ÷ BAC water added (mL). Then volume to draw (mL) = dose (mg) ÷ concentration, and a U-100 insulin syringe has 100 units per mL.
| Vial | BAC water | Concentration | Example draw |
|---|---|---|---|
| 5 mg | 1 mL | 5 mg/mL | 2 mg = 0.4 mL = 40 units |
| 10 mg | 2 mL | 5 mg/mL | 4 mg = 0.8 mL = 80 units |
| 10 mg | 1 mL | 10 mg/mL | 4 mg = 0.4 mL = 40 units |
| 20 mg | 2 mL | 10 mg/mL | 8 mg = 0.8 mL = 80 units |
- Add the diluent slowly down the inside wall of the vial — never squirt it onto the powder cake.
- Swirl gently until clear. Shaking can denature the peptide.
- Refrigerate once reconstituted and respect the beyond-use date on the bacteriostatic water.
- Double-check the decimal place. A 10× error on a milligram dose is the failure mode that actually hurts people.
Enter vial strength, diluent volume and your target dose and get the exact insulin syringe units to draw — no mental maths at the kitchen counter.
Open the peptide dosage calculatorRetatrutide vs tirzepatide vs semaglutide
| Compound | Receptors | Trial weight loss | Status |
|---|---|---|---|
| Retatrutide | GLP-1 + GIP + glucagon | ~24% at 48 weeks (12 mg) | Investigational |
| Tirzepatide | GLP-1 + GIP | ~21% at 72 weeks (15 mg) | Approved |
| Semaglutide | GLP-1 | ~15% at 68 weeks (2.4 mg) | Approved |
These trials were never run head to head, so treat the percentages as indications of scale rather than a ranking. The meaningful difference is regulatory: two of the three can be prescribed, monitored and sourced from a pharmacy. One cannot.
Side effects and what to watch
- Nausea, vomiting, diarrhoea and constipation — dose-escalation dependent.
- Dose-dependent heart rate increase observed across trial arms.
- Transient fasting glucose rises at the highest doses via glucagon agonism.
- Lean-mass loss alongside fat loss; protein intake and resistance training are not optional.
- Gastric emptying slows, which changes absorption of oral medications.
- Gallbladder issues and dehydration secondary to rapid weight loss and GI losses.
GLP-1-class compounds interact with insulin and sulfonylureas, oral contraceptives, thyroid medication and anything with a narrow absorption window. Run your full routine before adding one.
Open the interaction checkerFAQ
What is retatrutide?
Retatrutide (LY3437943) is an investigational triple agonist that activates the GLP-1, GIP and glucagon receptors. It is being studied by Eli Lilly for obesity and type 2 diabetes. It is not approved by the FDA, EMA, MHRA or TGA, and anything sold online as 'retatrutide' is an unregulated research chemical of unverified identity, purity and sterility.
What retatrutide doses were used in trials?
The Phase 2 obesity trial (NEJM, 2023) tested weekly subcutaneous doses of 1 mg, 4 mg, 8 mg and 12 mg, reached through a slow escalation over several months rather than started outright. Higher arms began at 2 mg and stepped up every 2–4 weeks. These are trial figures under medical supervision with monitoring — not a protocol to copy.
How is retatrutide titrated?
Trial titration was deliberately gradual because gastrointestinal side effects track dose escalation speed more than the final dose. Participants stayed at each step for at least 2–4 weeks before moving up, and steps were held or reduced when nausea, vomiting or dehydration appeared. Skipping steps is the most common cause of people abandoning a GLP-1-class compound.
How do you reconstitute retatrutide?
Lyophilised vials are reconstituted with bacteriostatic water. Concentration in mg/mL equals the vial strength in mg divided by the millilitres of BAC water added — so a 10 mg vial with 2 mL gives 5 mg/mL, and a 1 mg dose is 0.2 mL, which is 20 units on a U-100 insulin syringe. Add the diluent slowly against the vial wall, swirl rather than shake, and refrigerate once mixed.
Retatrutide vs tirzepatide — what's actually different?
Tirzepatide is a dual GLP-1/GIP agonist; retatrutide adds glucagon-receptor agonism, which raises energy expenditure on top of appetite suppression. In separate Phase 2 trials retatrutide's highest arm produced roughly 24% mean weight loss at 48 weeks versus about 21% for tirzepatide at 72 weeks. The trials were never run head to head, so the comparison is indirect. Tirzepatide is approved and prescribable; retatrutide is not.
Retatrutide vs semaglutide?
Semaglutide is a single GLP-1 agonist and the most established of the three, with approved obesity and diabetes indications plus cardiovascular outcome data. Retatrutide's trial weight-loss figures are higher, but it has no long-term safety record, no outcome data and no approval. More receptors also means more mechanisms that can misbehave.
What are the side effects?
Predominantly gastrointestinal: nausea, vomiting, diarrhoea and constipation, worst during escalation. Dose-dependent increases in heart rate were seen in trials, as were transient rises in fasting glucose at the highest doses via the glucagon arm. Muscle loss alongside fat loss is a real concern with this magnitude of weight reduction, which is why protein intake and resistance training matter.
Who should not use it?
Anyone with a personal or family history of medullary thyroid carcinoma or MEN2, prior pancreatitis, severe gastroparesis, active gallbladder disease, or who is pregnant, breastfeeding or planning pregnancy. GLP-1-class compounds also slow gastric emptying, which changes absorption of oral medications including oral contraceptives.
What monitoring makes sense?
Baseline and periodic fasting glucose and HbA1c, lipids, liver and kidney function, and resting heart rate. Weight and waist alone hide muscle loss — body composition or at least grip strength and lifting numbers give a better picture. Anyone using an unapproved compound should be doing this with a physician who knows about it.
Is retatrutide legal to buy?
It is not approved for human use anywhere. Vendors sell it labelled 'for research use only', which is a legal shield, not a quality guarantee. Third-party testing has repeatedly found research peptides that are underdosed, misidentified or contaminated. It is also prohibited in tested sport.
References & sources
Peer-reviewed trial publications and regulatory guidance cited on this page. Last reviewed 2026-07-30.
- Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389(6):514–526. https://pubmed.ncbi.nlm.nih.gov/37366315/
- Rosenstock J, Frias J, Jastreboff AM, et al. Retatrutide in people with type 2 diabetes: a randomised, double-blind, placebo- and active-controlled, phase 2 trial. Lancet. 2023;402(10401):529–544. https://pubmed.ncbi.nlm.nih.gov/37385280/
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387(3):205–216. https://pubmed.ncbi.nlm.nih.gov/35658024/
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384(11):989–1002. https://pubmed.ncbi.nlm.nih.gov/33567185/
- U.S. Food and Drug Administration. Medications Containing Semaglutide Marketed for Type 2 Diabetes or Weight Loss — compounded and unapproved product warnings. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/medications-containing-semaglutide-marketed-type-2-diabetes-or-weight-loss
Track GLP-1 cycles properly in DoseRoutine
Reconstitution maths, titration schedules, vial inventory, injection-site rotation and blood-work trends in one place.
Start free trialEducational reference only, not medical advice. Retatrutide is not an approved medicine — do not start, stop or combine any protocol without a qualified physician.