Retatrutide
LY3437943 · Triple-G
Investigational triple agonist targeting GIP, GLP-1, and glucagon receptors simultaneously.
Class
GIP / GLP-1 / glucagon triple receptor agonist
Half-life
~6 days (once-weekly dosing)
Evidence
Limited human data
Limited human data
Small open-label studies, case series, or trials in a narrow population. Directionally informative, not conclusive.
Overview
Retatrutide adds glucagon receptor agonism to the GIP/GLP-1 combination. That third arm is the interesting one: glucagon raises energy expenditure and drives hepatic fat oxidation, so instead of working purely by suppressing intake, retatrutide also appears to increase the amount of energy burned.
Phase 2 results were striking — a mean 24.2% body weight reduction at 48 weeks on 12 mg weekly, with the weight-loss curve still declining at study end rather than plateauing. A separate phase 2 study reported roughly 86% relative reduction in liver fat content in people with MASLD.
It is not approved anywhere. Phase 3 trials are ongoing. Everything sold under this name outside a clinical trial is a research chemical of unverified identity and purity, and the long-term safety profile — particularly the cardiovascular consequences of chronic glucagon receptor agonism — is genuinely unknown.
How it works
- GLP-1 agonism — appetite suppression, delayed gastric emptying, glucose-dependent insulin secretion.
- GIP agonism — improved insulin sensitivity and adipose lipid handling.
- Glucagon receptor agonism — increased resting energy expenditure and hepatic fatty-acid oxidation, the mechanistic differentiator from dual agonists.
- The combination produces both reduced intake and increased expenditure, which is why effect sizes exceed dual agonists.
What the research shows
Researched effects
- Mean 24.2% body weight reduction at 48 weeks (phase 2, 12 mg)
- ~86% relative reduction in liver fat content in MASLD (phase 2)
- HbA1c reduction comparable to or exceeding tirzepatide in type 2 diabetes cohorts
- Weight-loss trajectory had not plateaued at 48 weeks, unlike dual agonists
Limitations & what it won't do
- No phase 3 efficacy or safety data published. No regulatory approval in any jurisdiction.
- Glucagon agonism raises heart rate — mean increases of 6–10 bpm were seen in phase 2, with unknown long-term cardiovascular consequence.
- Dose-dependent GI effects were more frequent than with tirzepatide at comparable weight-loss magnitudes.
- Grey-market material has no purity guarantee; independent testing of research-chemical peptides routinely finds under-dosed or misidentified product.
Dosing protocols
These ranges reflect published trials and community protocols. They are reference information, not a prescription. Doses are per injection unless noted.
Phase 2 trial titration (reference only)
2 mg → 12 mgTrial schedule was 2 mg for 4 weeks, then escalating in 2–4 mg steps every 4 weeks. This is documented for reference — it is a clinical-trial protocol, not a usage recommendation.
Low-dose phase 2 arm
1 mg → 4 mgLower arms still produced double-digit weight reduction with a milder side-effect burden.
Reconstitution & measuring your dose
Handling
- Typical vial sizes
- 10 · 15 · 20 · 30 · 40 · 50 · 60 mg
- Suggested BAC water
- 2 mL
- Storage
- Lyophilised powder refrigerated at 2–8 °C, protected from light.
- After reconstitution
- Reconstituted: approximately 28 days refrigerated. Do not freeze.
Why 2 mL? A 20 mg vial in 2 mL yields 10 mg/mL — 2 mg lands on 20 units and 12 mg on 100 units of a U-100 syringe, keeping the whole titration on whole-number marks.
Dose calculator
Draw to
26.7units
= 0.267 mL · 75 mcg per unit
Concentration
7500 mcg/mL
Doses per vial
7
Side effects
Common
- Nausea and vomiting, dose-dependent
- Diarrhoea and constipation
- Increased resting heart rate (mean +6–10 bpm in phase 2)
- Decreased appetite, sometimes severe
- Fatigue
Serious / rare
- Unknown long-term cardiovascular risk from sustained glucagon agonism and elevated heart rate
- Acute pancreatitis (incretin class signal)
- Gallbladder disease
- Hyperglycemia risk in theory from glucagon agonism, though offset by incretin arms in trials
Contraindications & interactions
Do not use if you have
- Medullary thyroid carcinoma or MEN2 (personal or family)
Same rodent thyroid C-cell signal as the rest of the incretin class. Absolute contraindication.
- Pregnant, breastfeeding, or trying to conceive
No pregnancy safety data whatsoever. Absolute contraindication.
- Pancreatitis history
Incretin-class pancreatitis signal; prior pancreatitis is a contraindication.
- Cardiovascular disease
Sustained heart-rate elevation from glucagon agonism with no cardiovascular outcomes data makes established cardiovascular disease an unacceptable risk here.
- Arrhythmia or palpitations
Documented resting heart-rate increase is directly additive to an existing rhythm disorder.
Use caution if you have
- High blood pressure
Heart-rate elevation in an already hypertensive cardiovascular system warrants close monitoring.
- Gastroparesis or delayed gastric emptying
Delayed gastric emptying is additive with existing gastroparesis.
- Gallbladder disease or gallstones
Rapid weight loss substantially increases gallstone risk.
- Type 1 diabetes
Glucagon agonism in type 1 diabetes is a poorly characterised risk.
- Liver disease
Studied in MASLD with benefit, but established liver disease requires clinician oversight.
Medication interactions
- avoidInsulin — Hypoglycemia risk requiring supervised insulin reduction, with the added complication of glucagon agonism.
- avoidSulfonylureas — Additive hypoglycemia risk.
- avoidGLP-1 / GIP agonists — Retatrutide already includes GLP-1 agonism. Never stack.
- cautionBlood pressure medication — Heart-rate elevation may work against rate-controlling agents like beta blockers.
- avoidStimulants — Additive heart-rate and blood-pressure elevation on top of an already documented chronotropic effect.
Don't stack with
- Semaglutide — Duplicate GLP-1 agonism.
- Tirzepatide — Duplicate GLP-1 and GIP agonism.
- Liraglutide — Duplicate GLP-1 agonism.
- Melanotan II — Both raise cardiovascular strain; combined heart-rate and pressure effects are unstudied.
What to monitor
- Resting heart rate and blood pressure weekly — this is the specific signal to watch
- HbA1c and fasting glucose
- Liver enzymes and, where available, hepatic fat imaging
- Body composition to track lean mass
- Third-party purity testing of any research-sourced material
References
- Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 TrialNEJM 2023;389:514-526
- Retatrutide for MASLD — Phase 2 substudyNature Medicine 2024
Research & educational information only — not medical advice.
You must be 18 or older to use this site. The peptides described are presented as research chemicals intended for research purposes only. Most are not approved by the FDA for human use. Dosing ranges reflect what has appeared in the scientific literature or community protocols and are not prescriptions. Nothing here replaces evaluation by a licensed physician who knows your full medical history.
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