Compounds / Retatrutide
Retatrutide
Also known as: LY3437943, CAS 2381089-83-2
Primary research focus: Obesity and type 2 diabetes (metabolic)
Last updated July 2026 · Reviewed against FDA labeling and published research.
What is Retatrutide?
Retatrutide is a first-in-class, once-weekly investigational peptide that activates three metabolic receptors at once: GIP, GLP-1, and glucagon. Developed by Eli Lilly, this "triple agonist" pairs the appetite and glucose control of GLP-1/GIP with the increased energy expenditure of glucagon, and has produced the largest weight reductions reported for an injectable obesity drug in Phase 3 trials to date.
It simultaneously activates the GLP-1 receptor (appetite suppression and glucose-dependent insulin secretion), the GIP receptor (insulin sensitivity and appetite regulation), and the glucagon receptor (increased energy expenditure and hepatic fat mobilization). The added glucagon activity is what distinguishes it from dual agonists such as tirzepatide and is thought to drive its greater weight-loss magnitude.
How it’s supplied
Investigational and not commercially available. Retatrutide is not FDA-approved and cannot be obtained by prescription as of July 2026. In clinical trials it is given as a once-weekly subcutaneous injection. There is no approved brand name or commercial formulation. Any material encountered outside of a clinical trial is unregulated and not quality-assured.
Dosage Chart
Units shown are for a U-100 insulin syringe (100 units = 1 mL), calculated from the vial size and BAC water you select. Always confirm against your prescription and your syringe markings.
| Phase | Dose | Frequency | Notes |
|---|---|---|---|
| Weeks 1-4 | 2mg | 1x Weekly | — |
| Weeks 4-8 | 4mg | 1x Weekly | — |
| Weeks 8-12 | 6mg | 1x Weekly | — |
| Weeks 12-16 | 9mg | 1x Weekly | — |
| Weeks 17+ | 12mg | 1x Weekly | — |
- Administer on the same day each week to maintain stable plasma levels
- Titrate slowly; gastrointestinal effects are dose-related and ease with gradual escalation
- Rotate injection sites to reduce irritation and lipohypertrophy
- Reduce dose when combined with insulin or sulfonylureas to lower hypoglycemia risk
- Discuss pausing before scheduled surgery or anesthesia (delayed gastric emptying)
- Maintain hydration to offset gastrointestinal fluid loss
- Not for use during pregnancy or breastfeeding
- Do not exceed the recommended dose to try to speed results
Potential Benefits and Side Effects
Effects reported in published research. Not a promise of results, and not medical advice.
- Substantial weight loss: up to about 28-30% of body weight in Phase 3 obesity trials, the largest reported for an injectable to date.
- Improved glycemic control: HbA1c reductions up to about 2.0% in type 2 diabetes.
- Reduced knee osteoarthritis pain and improved physical function (TRIUMPH-4).
- Improved obstructive sleep apnea severity (TRIUMPH-1 substudy).
- Broad cardiometabolic improvements, including blood pressure, lipids, and liver fat.
- Nausea, vomiting, diarrhea, and constipation (dose-related, usually mild to moderate).
- Dysesthesia (altered skin sensation), generally mild to moderate and dose-related.
- Urinary tract infections.
- Increased resting heart rate.
- Injection-site reactions.
- Hypoglycemia when combined with insulin or sulfonylureas.
- Discontinuation due to adverse events was dose-related (about 4-11% across 4/9/12 mg in TRIUMPH-1).
Warnings and contraindications
Important safety information. This is not exhaustive — read the full prescribing information and consult your prescriber or pharmacist.
- Investigational drug: there is no FDA-approved prescribing information. The items below are drawn from trial observations and the known effects of the incretin/glucagon drug class.
- Thyroid C-cell tumors: GLP-1 receptor agonists cause thyroid C-cell tumors in rodents, and approved analogs carry a boxed warning. Human relevance is unconfirmed, but the class precaution applies.
- Gastrointestinal effects: nausea, vomiting, diarrhea, and constipation are common and dose-related; most are mild to moderate and improve with slow dose escalation.
- Pancreatitis: acute pancreatitis has been associated with the incretin class; stop use and seek care if suspected.
- Gallbladder disease: rapid weight loss and incretin therapy are linked to gallstones and cholecystitis.
- Increased heart rate: the glucagon component can raise resting heart rate.
- Hypoglycemia: risk rises when combined with insulin or insulin secretagogues (sulfonylureas).
- Diabetic retinopathy: rapid glucose improvement has been linked to transient worsening of retinopathy in this class.
- Dysesthesia: altered skin sensation was reported in retatrutide trials, generally mild to moderate, dose-related, and usually resolving during treatment.
- Dehydration and kidney injury: fluid loss from GI effects can cause dehydration and acute kidney injury, especially with diuretics or ACE inhibitors/ARBs.
- Personal or family history of medullary thyroid carcinoma (MTC).
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- Known serious hypersensitivity to retatrutide or any of its components.
- Pregnancy and breastfeeding (class caution; not studied, and weight-loss agents are generally avoided in pregnancy).
- Note: these mirror the labeled contraindications of approved GLP-1 analogs and are applied to retatrutide by drug class. They are not established retatrutide-specific labeling, because the drug is investigational.
Reconstitution Steps
How to prepare the lyophilized vial. Confirm specifics with your pharmacist or prescriber.
- Let both the lyophilized vial and the bacteriostatic water reach room temperature before starting.
- Wipe the vial stopper and the BAC water vial with a fresh alcohol swab.
- Draw your chosen volume of bacteriostatic water into the syringe.
- Inject the water slowly down the inside wall of the vial, not directly onto the powder.
- Swirl gently to dissolve; do not shake. The solution should turn clear.
- Label the vial with the date and store it refrigerated.
US regulatory status
Classifications are public record but can change. For reference only, not legal advice.
Development: Investigational (Eli Lilly). Global Phase 3 TRIUMPH registrational program, plus a separate TRANSCEND-T2D diabetes program. TRIUMPH-4 (obesity plus knee osteoarthritis) reported December 2025: 28.7% mean weight loss at 68 weeks on 12 mg. TRIUMPH-1 (obesity, N=2,339) confirmed May 21, 2026: 28.3% at 80 weeks on 12 mg, up to 30.3% at 104 weeks in a BMI >=35 extension, with 45.3% achieving >=30% weight loss. TRANSCEND-T2D-1 (type 2 diabetes) published in The Lancet June 2026: up to -2.0% HbA1c and 16.8% weight loss at 40 weeks. TRIUMPH-2 (obesity plus T2D) and TRIUMPH-3 (obesity plus established cardiovascular disease) are expected later in 2026. Industry estimates anticipate a U.S. NDA filing around Q4 2026. Not approved for any indication as of July 2026. Verify current status against ClinicalTrials.gov and Eli Lilly disclosures.
Notes: Cannot be legally compounded under section 503A or 503B: retatrutide has no USP/NF monograph, is not a component of an FDA-approved drug, and has never appeared on the FDA drug shortage list. Compounding eligibility would likely change only upon FDA approval (industry estimates around 2027).
International status
Pharmacokinetics
Storage and handling
Important Notes
Practical considerations for consistency and safety.
- Titrate slowly. Gastrointestinal effects are strongly dose-related and ease with gradual escalation.
- Once-weekly dosing on the same day each week supports steady levels given the ~6-day half-life.
- Never freeze reconstituted solution.
Lifestyle Factors
- Studied as an adjunct to a reduced-calorie diet and increased physical activity.
- Adequate protein and resistance training help preserve lean mass during rapid weight loss.
- Maintain hydration to offset gastrointestinal fluid losses.
References
Related compounds
Important disclaimer
This page is an educational reference, not medical advice, a diagnosis, or a treatment recommendation, and not a substitute for your prescriber or pharmacist. Approval and regulatory status varies by compound and can change. Always confirm against current prescribing information and consult a qualified healthcare professional before making any decision about a medication.