Retatrutide¶

Tags: Weight Loss, Diabetes, Triple-agonist

Quick facts¶

• Typical Dose: 0.5–12 mg weekly
• How Often: Once weekly
• Route: Injectable — subcutaneous (abdomen, thigh, upper arm); rotate sites weekly to prevent lipodystrophy
• Cycle: Continuous therapy (effects reverse on discontinuation)
• Storage: 2–8°C (refrigerated)

Overview¶

Retatrutide (LY3437943) is a novel triple hormone receptor agonist targeting GLP-1, GIP, and glucagon receptors. Phase II trials achieved 24.2% weight loss at 48 weeks — the highest recorded for any obesity medication. Currently in Phase III development by Eli Lilly for obesity and type 2 diabetes treatment.

Key Benefits¶

• Triple hormone receptor activation provides superior weight loss (24.2%), improved glycemic control, and enhanced cardiovascular benefits compared to single or dual agonists.

Mechanism of action¶

Activates GLP‑1 for appetite suppression, GIP for insulin sensitivity, and glucagon for increased energy expenditure and hepatic fat oxidation.

Molecular information¶

• Weight: 4,731.33 Da
• Length: 39 amino acids
• Type: Triple GLP‑1/GIP/glucagon agonist

Amino acid sequence:

His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser

C20 fatty acid conjugation with Aib residues for DPP‑4 resistance

Research indications¶

• Weight Loss — Most Effective: clinical trials show 17.5% at 24 weeks and 24.2% at 48 weeks
• Diabetes — Effective: improved glycemic control and HbA1c reductions
• Cardiovascular — Moderate: improvements observed in metabolic and liver fat endpoints

Research protocols¶

Timing: Administer on the same day each week for consistent hormone regulation. Can be taken with or without food due to subcutaneous administration.

Interactions¶

How to reconstitute¶

1. Remove Retatrutide vial from refrigeration and allow to reach room temperature (15–20 minutes).
2. Clean vial top with alcohol swab and allow to air dry completely.
3. Add calculated amount of bacteriostatic water slowly down the side of the vial to minimize foaming.
4. Gently swirl the vial in circular motions — DO NOT shake vigorously as this may damage the peptide structure.
5. Allow to fully dissolve (may take 2–3 minutes); solution should be clear and colorless.
6. Store reconstituted solution refrigerated (2–8°C) and use within 28 days.
7. Draw calculated dose using an appropriate syringe and inject subcutaneously into abdomen, thigh, or upper arm.
8. Rotate injection sites weekly to prevent lipodystrophy and maintain absorption consistency.

Quality Indicators¶

What to expect¶

• Week 1–2: Initial appetite suppression and mild GI effects as body adapts
• Week 2–4: Noticeable reduction in cravings and early weight loss (2–5%)
• Week 4–8: Significant appetite control and steady weight loss (5–10%)
• Week 8–16: Substantial weight reduction (10–18%) with metabolic improvements
• Week 16–24: Major weight loss milestones (15–22%) and liver fat reduction
• Week 24–48: Maximum clinical efficacy (20–24.2%) with comprehensive metabolic improvements

Side effects & safety¶

• Most common: gastrointestinal (nausea, vomiting, diarrhea) — typically mild to moderate and dose‑dependent
• Start conservatively (0.5 mg weekly) to minimize GI effects; escalate every ~4 weeks
• Monitor for pancreatitis (severe abdominal pain) and discontinue if suspected
• Monitor heart rate and cardiovascular status during dose escalation
• Contraindicated with personal/family history of medullary thyroid carcinoma or MEN2
• May cause rapid weight loss — monitor and adjust dose if needed

References¶