Retatrutide

Retatrutide, also known as LY3437943, is an investigational Eli Lilly drug that activates GLP-1, GIP and glucagon receptors together. Its Phase III development program investigates obesity and metabolic disorders. In December 2025, TRIUMPH-4 results at 68 weeks showed an average 28.7% reduction in body weight with 12 mg, equivalent to 71.2 lbs from an initial 248.5 lbs. That result exceeded previously reported weight-loss efficacy for obesity medicines at that time. Retatrutide has no FDA approval, and FDA restrictions prevent lawful compounding under either 503A or 503B.

• Weight Loss

  Most effective

  Clinical trials show substantial reductions in body weight with benefits that persist over follow-up.

• Blood Sugar Control

  Most effective

  Research examines improved glucose regulation and reduced A1C in people with type 2 diabetes.

  Human, randomised · 1 reference

• Cardiovascular Health

  Effective

  Research addresses fewer cardiovascular events among people at elevated risk.

• Metabolic Syndrome

  Effective

  Potential metabolic benefits involve several components of metabolic syndrome at once.

These are commonly discussed research protocols — not medical advice. Consult a healthcare provider before use.

• Other GLP-1 agonists (semaglutide, tirzepatide)

  Avoid

• Insulin

  Monitor

• Sulfonylureas

  Monitor

• Metformin

  Compatible

• SGLT2 Inhibitors

  Compatible

• Oral Contraceptives

  Caution

• Warfarin / Blood Thinners

  Monitor

• NAD+

  Compatible

Diluent: Use bacteriostatic water; avoid saline because it may cause precipitation.

1. Let your refrigerated Retatrutide vial warm to room temperature for 15–20 minutes before preparation.
2. Disinfect the vial’s rubber closure with an alcohol wipe, then wait until it has dried completely.
3. Use a sterile syringe to measure the calculated amount of bacteriostatic water. Avoid saline because precipitation may occur.
4. Add the water slowly against the vial’s inner wall. Keep the stream away from the dry powder itself.
5. Rotate the vial gently to mix its contents. Do not shake forcefully, because this can damage the peptide.
6. Wait 2–3 minutes for the powder to dissolve completely. Check that the liquid is transparent and has no color.
7. Measure your calculated subcutaneous dose with an insulin syringe after dissolution.
8. Choose the abdomen, upper arm or thigh for injection. Alternate the injection location each time to help prevent lipodystrophy.
9. Refrigerate the mixed solution at 2–8°C, and discard any remainder after 28 days. Use these steps only for an appropriate research formulation; follow the specific product instructions for prescription presentations.

Week 1–2

Appetite may start to decline. Mild nausea or a sense of fullness can accompany the initial adjustment.

Week 2–4

Cravings and meal portions may become noticeably smaller, with the first changes in body weight.

Week 4–8

Appetite control may strengthen as weight declines steadily; glucose regulation may also improve when relevant.

Week 8–16

Larger weight changes and greater energy may develop, while metabolic measurements begin to improve.

Week 16–24

Further weight-loss milestones may coincide with cardiovascular benefits and improvements in lipid measurements.

Week 24+

Sustained benefit and broader metabolic improvements may develop toward maximal efficacy. Timing varies, and trial endpoints extend beyond this interval.

• Nausea, usually temporary and more pronounced at higher doses · Most common; 43% at 12 mg
• Loose stools or constipation while increasing the dose · Diarrhea: 33% at 12 mg
• Vomiting, especially during initiation or upward dose adjustments
• Less appetite and feeling full earlier during meals
• Bruising or redness around the injection area
• Tiredness, particularly during the first weeks
• Pancreatitis; stop use immediately if severe abdominal pain develops · Rare
• Thyroid C-cell effects · Rare
• Dysesthesia, or altered sensations of touch, in TRIUMPH-4 participants receiving 9–12 mg · 8.8–20.9%
• Stopping treatment because of adverse events in TRIUMPH-4 · 12.2% at 9 mg; 18.2% at 12 mg

Contraindications

• Avoid use with MEN2 or a history of thyroid cancer.

Retatrutide: investigational in the US; 503A compounding banned.

• US

  Investigational

  FDA — Investigational Phase III drug without US approval. Lawful compounding is not available under sections 503A or 503B, and prescription access through telehealth is unavailable.

  Rx required

  No

  503A

  Banned

  Telehealth

  No

1. 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 conducted in the USA. (2023)

   PMID 37385280DOI 10.1016/S0140-6736(23)01053-X

2. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. (2023)

   PMID 37366315DOI 10.1056/NEJMoa2301972

3. Retatrutide-A Game Changer in Obesity Pharmacotherapy. (2025)

   PMID 40563436DOI 10.3390/biom15060796

4. Retatrutide obesity studies on ClinicalTrials.gov (2024)

5. Retatrutide studies on ClinicalTrials.gov (2024)