Retatrutide
Retatrutide is the heaviest hitter in this catalog. It works three hunger and metabolism switches at once: the two tirzepatide already uses, plus a third that pushes the body to burn more rather than only eat less. People come to it when a GLP-1 stalled out or was never enough, and it produces the largest weight-loss numbers reported anywhere on this site. Dosed once a week.
What it does
When a GLP-1 stalled out
The main reason people run retatrutide. You were on semaglutide or tirzepatide, the loss flattened, and stepping the dose up did not move it again. Retatrutide adds a third switch the others do not touch, aimed at raising what you burn rather than only lowering what you eat. In its lead trial the top dose averaged 22% loss over 48 weeks, with about 85% of people losing at least a tenth of their body weight. Nobody taking it has regulatory cover; it is approved nowhere.
Sources: Jastreboff AM, et al., 2023
Burning, not just eating less
The third switch is the glucagon receptor, and it is what separates retatrutide from everything else here. GIP and GLP-1 work mostly on appetite. Glucagon leans on energy expenditure, so the body spends more instead of only wanting less. That is the proposed reason its numbers run ahead of the dual and single-receptor drugs.
Sources: PMC review, Retatrutide, 2025
Blood sugar and liver fat
Beyond weight, people run it for the metabolic clean-up that tends to follow. Up to 82% of people with type 2 diabetes in a 36-week trial brought their HbA1c under 6.5%, and it is being studied for the fatty-liver disease that travels with obesity. The phase 3 programme wrapped this year and none of it is published yet.
Sources: Rosenstock J, et al., 2023, Triple hormone receptor, 2024
Dosing
Community reportedCommunity titration, standard approach (peptidedosages.com)2 mg to 8 mg, weekly
| Timeframe | Dosage | Frequency | Note |
|---|---|---|---|
| Weeks 1-4 | 2 mg | weekly | Starting dose1 |
| Weeks 5-8 | 4 mg | weekly | |
| Weeks 9-12 | 6 mg | weekly | |
| Weeks 13+ | 8 mg | weekly | Maintenance |
- peptidedosages.com's own standard-approach schedule; not derived from a controlled human dose-ranging trial of this specific titration path, though the numbers align with the Phase 2 trial doses reported in Full research.
Community reportedCommunity titration, advanced approach (peptidedosages.com)2 mg to 12 mg, weekly
| Timeframe | Dosage | Frequency | Note |
|---|---|---|---|
| Weeks 1-4 | 2 mg | weekly | Starting dose |
| Weeks 5-8 | 4 mg | weekly | |
| Weeks 9-12 | 8 mg | weekly | |
| Weeks 13+ | 12 mg | weekly | Site's maximum1 |
- The site's own upper-end schedule; 12 mg matches the highest dose tested in the Phase 2 trials in Full research, but this titration path itself is peptidedosages.com's community characterization, not trial-derived.
Primary structure
No sequence recorded for this compound.
Full research
Evidence tier
Human trials, not approved for this use
Retatrutide has completed, published, peer-reviewed phase 2 randomized controlled trials in obesity and type 2 diabetes (both cited in this entry with PMID/DOI) but holds no FDA or EMA approval for any indication. Its phase 3 programme is no longer ongoing: as of 19 August 2026 at least six retatrutide phase 3 studies are registered as completed on ClinicalTrials.gov, with completion dates between November 2025 and June 2026, covering obesity, obesity with cardiovascular disease, and type 2 diabetes. Topline results have been reported by the sponsor but are not cited here as effect sizes, because this entry records only figures it can verify against a primary published source, and the phase 3 results are not yet peer-reviewed publications.
Original dosing schedule
The Dosing table above this section now shows a community- or vendor-sourced schedule (peptidedosages.com). The regulatory-label or clinical-trial dosing this entry was originally built on is kept here, unchanged, rather than removed.
Clinical trial
| Timeframe | Dosage | Frequency | Note |
|---|---|---|---|
| Weeks 1-4 | 2 mg | weekly | Starting dose1 |
| Weeks 5-8 | 4 mg | weekly | |
| Weeks 9-12 | 6 mg | weekly | |
| Weeks 13+ | 8 mg | weekly | Maintenance2 |
- Trial-reported dosing from Phase 2 obesity and type 2 diabetes trials (Jastreboff et al., NEJM 2023; Rosenstock et al., Lancet 2023); not FDA-approved prescribing information. No fixed escalation interval or maximum is established outside the trial protocol.
- Reported trial data associate 8-12 mg doses with 22-24% body-weight loss at 48 weeks.
Clinical trial
| Timeframe | Dosage | Frequency | Note |
|---|---|---|---|
| Weeks 1-4 | 2 mg | weekly | Starting dose1 |
| Weeks 5-8 | 4 mg | weekly | |
| Weeks 9-12 | 8 mg | weekly | |
| Weeks 13+ | 12 mg | weekly | Trial maximum2 |
- Trial-reported dosing from the same Phase 2 program; not FDA-approved prescribing information. No fixed escalation interval or maximum is established outside the trial protocol.
- 12 mg is the highest dose tested in the cited Phase 2 program, not an FDA-approved maximum.
Identity
| Full name | Retatrutide is not approved by the FDA or any other regulatory agency for any indication; it is an investigational compound (development code LY3437943), a synthetic 39-amino-acid single-molecule peptide engineered from a GIP peptide backbone, conjugated to a fatty diacid moiety for albumin binding. Molecular weight approximately 4,731.3 to 4,731.4 Da (formula C221H342N46O68, CAS 2381089-83-2), per chemical-vendor and database sources rather than an FDA label, since none exists; these figures are consistent across multiple independent chemical-supplier sources. All dosing in this entry is trial-reported, not prescribing information, and must never be presented as a clinical dose. |
|---|---|
| Class | GIP/GLP-1/glucagon receptor triple agonist, investigational |
Mechanism of action
Plain language
Retatrutide activates three different gut and pancreas hormone receptors at once, the two that semaglutide and tirzepatide use, plus a third (glucagon) that increases the body's resting energy burn. That third receptor is the reason it is being investigated for larger weight-loss effect sizes than dual or single agonists.
Technical
Retatrutide is a triple agonist at the GIP receptor (GIPR), GLP-1 receptor (GLP-1R), and glucagon receptor (GCGR). In vitro cell-based potency data (EC50) reported in a 2025 review show it is most potent at GIPR (EC50 0.0643 nM), intermediate at GLP-1R (EC50 0.775 nM), and least potent at GCGR (EC50 5.79 nM), weaker than native glucagon at its own receptor but still active enough at typical trial doses to drive the increased energy expenditure associated with glucagon receptor agonism. GCGR activation is the mechanistic differentiator from GLP-1-only and GIP/GLP-1 dual agonists: it increases hepatic glucose output and lipid oxidation, offset by the insulinotropic GIP/GLP-1 effects, but adds a thermogenic, energy-expenditure component not present in semaglutide or tirzepatide.
Sources: PMC review, Retatrutide, 2025
What it’s used for
Human trials, not approved for this use
- Obesity, without diabetes: phase 2 randomized controlled trial, 48 weeks, doses of 1, 4, 8, and 12 mg weekly (with 2 mg or 4 mg starting/lead-in doses at the higher levels). Placebo-adjusted mean weight reduction of 16% at 24 weeks and 22% at 48 weeks with the 12 mg dose; approximately 85% of 12 mg participants achieved at least 10% weight loss, 45% achieved at least 20%.
Sources: Jastreboff AM, et al., 2023
- Type 2 diabetes: phase 2 randomized controlled trial, 36 weeks, 281 participants randomized to 0.5, 4, 8, or 12 mg retatrutide, dulaglutide 1.5 mg, or placebo. HbA1c below 6.5% achieved in up to 82% of participants; body weight reduction up to 17% at the 8-12 mg doses.
Sources: Rosenstock J, et al., 2023
- Metabolic dysfunction-associated steatotic liver disease (MASLD, liver fat): phase 2a randomized controlled trial.
Sources: Triple hormone receptor, 2024
- Body composition substudy in type 2 diabetes, examining fat mass versus lean mass changes.
Sources: Retatrutide body composition, 2025
Off-label / community use
- Retatrutide is sold exclusively through research-chemical and compounding channels in the absence of any approval; every use in a human being outside a registered clinical trial is by definition off-label and unsupervised, with no controlled human dosing data outside the phase 2 trials. Community dosing practice is anecdotal and directly extrapolated from the trial doses without the trial's medical supervision, lab monitoring, or controlled titration criteria.
Sources: Jastreboff AM, et al., 2023
Pharmacokinetics
| Half-life |
Systematic review approximately 6 days, supporting once-weekly dosing Sources: PMC review, Retatrutide, 2025 |
|---|---|
| Time to peak (Tmax) |
Systematic review approximately 12-72 hours post-dose Sources: PMC review, Retatrutide, 2025 |
| Metabolism |
Systematic review primarily proteolytic/hepatic; no meaningful cytochrome P450 interaction reported Sources: PMC review, Retatrutide, 2025 |
| Route |
Systematic review subcutaneous injection (trial administration) Sources: PMC review, Retatrutide, 2025 |
Reconstitution
| Vial strength | 20 mg (commonly advertised compounded/research vial; vendors also list 10, 30, 40, and 60 mg vials) |
|---|---|
| Diluent | Bacteriostatic water |
| Diluent volume | 2 mL |
| Concentration | 10 mg/mL |
Sources: Bolt Pharmacy UK, Great Northern Peptides, Glunovabio retatrutide mixing
Dose calculator
Enter a vial strength, diluent volume, and desired dose to see the resulting concentration, dose volume, and units on a standard U-100 insulin syringe. Nothing entered here is saved, stored, or sent anywhere – the calculation runs only in your browser.
This calculator needs JavaScript. The arithmetic it runs is: concentration = vial strength in mg divided by diluent volume in mL; dose volume in mL = dose in mg divided by concentration; units on a U-100 syringe = dose volume in mL times 100.
Storage and post-reconstitution stability
Unopened storage
No FDA-approved product exists. Lyophilized research/compounded vials are stored per vendor instructions, generally refrigerated before reconstitution; see reconstitution and post_reconstitution_stability for the only sourced handling data.
Post-reconstitution stability – Vendor claim
28-30 days refrigerated when bacteriostatic water is used; vendors claim non-bacteriostatic (sterile, preservative-free) water reconstitutions should be used within 24-48 hours. 2-8C, refrigerated
Sources: GLP3 Planner retatrutide
No citable figure. These are commercial vendor claims with no regulatory validation; no FDA or equivalent regulatory stability data exists because no approved retatrutide product exists.
Safety
Notable risks
- No FDA boxed warning exists because there is no approved label. Retatrutide shares the mechanistic GLP-1/GIP-agonist class concern for thyroid C-cell tumors seen in rodent studies of semaglutide, tirzepatide, and liraglutide; whether this rodent finding applies to retatrutide specifically has not been addressed by a citable source, and this gap is stated rather than filled. No contraindication language for retatrutide could be sourced because no approved label exists to state one.
Sources: PMC review, Retatrutide, 2025
- Gastrointestinal adverse events (nausea, diarrhea, vomiting, constipation) were the most common trial-reported adverse effects, were dose-related, were mostly mild to moderate, and were partially mitigated by a lower (2 mg vs. 4 mg) starting dose. Dose-dependent increases in heart rate were observed, peaking around 24 weeks and declining thereafter.
Sources: Jastreboff AM, et al., 2023
- A separate review reported gastrointestinal-driven trial discontinuation rates in the range of 20-50% within the first year across dose groups, and noted less frequent elevated ALT and skin hyperesthesia.
Sources: PMC review, Retatrutide, 2025
- No FDA-mandated monitoring exists because there is no approved label. Trial protocols included standard gastrointestinal adverse-event tracking, heart-rate monitoring, and liver enzyme checks; anyone using retatrutide outside a supervised trial has no equivalent structured monitoring, which is itself a safety gap worth stating plainly rather than glossing over.
Sources: Jastreboff AM, et al., 2023
Sources
- Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526. doi:10.1056/NEJMoa2301972 (2023)
- Rosenstock 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. Lancet. 2023;402(10401):529-544. doi:10.1016/S0140-6736(23)01053-X (2023)
- Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine. 2024 (2024)
- Retatrutide body composition substudy in type 2 diabetes, Lancet Diabetes & Endocrinology 2025 (2025)
- PMC review, Retatrutide: A Game Changer in Obesity Pharmacotherapy (2025)
- Bolt Pharmacy UK, retatrutide bacteriostatic-water reconstitution guide (commercial)
- Great Northern Peptides, retatrutide dosing guide for researchers (commercial)
- Glunovabio retatrutide mixing guide (commercial)
- GLP3 Planner retatrutide reconstitution guide (commercial)
- Chemical-vendor and database sources for retatrutide molecular data (MedChemExpress data sheet; also ChemicalBook and KEGG DRUG D12430)
- peptidedosages.com, Retatrutide 10 mg vial dosage protocol
This is a research and educational reference, not medical advice. Nothing on this site is a recommendation to use any compound.