Retatrutide Dosage Guide

Retatrutide is an investigational once-weekly injectable peptide developed by Eli Lilly that simultaneously activates three hormone receptors: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors. This triple-agonist mechanism represents the next evolution beyond dual agonists like tirzepatide.

The Phase 2 trial published in the New England Journal of Medicine (2023) demonstrated dose-dependent weight loss of up to 24.2% at the 12 mg dose over 48 weeks — the highest ever reported for a pharmacological agent. The glucagon receptor activation uniquely promotes energy expenditure and hepatic fat reduction in addition to appetite suppression.

Dosing is based on Phase 2 trial data. Retatrutide uses a dose-escalation protocol:

Weight loss was dose-dependent in the Phase 2 trial: 8.9% (1 mg maintenance), 17.1% (4 mg escalated to 8 mg), and 24.2% (4 mg escalated to 12 mg) at 48 weeks. The escalation schedule is critical for minimizing GI side effects.

Retatrutide is administered once weekly by subcutaneous injection:

• Consistent day: Inject on the same day each week.
• Any time of day: Can be administered regardless of meals.
• Dose escalation: Increase dose every 4 weeks per the titration schedule. If significant GI side effects occur, maintain the current dose level for an additional 4 weeks before escalating.

Duration: The Phase 2 trial ran for 48 weeks. Weight loss appeared to still be progressing at study end for the higher dose groups, suggesting longer treatment durations may yield additional benefit. Phase 3 trials are ongoing.

Retatrutide is currently only available through clinical trials as pre-filled devices. For compounded research formulations:

• Step 1: Swab vial stoppers with alcohol.
• Step 2: Reconstitute with the appropriate volume of BAC water per vial specifications.
• Step 3: Direct stream along glass wall. Allow to dissolve naturally.
• Step 4: Gently swirl until clear.
• Step 5: Store at 2–8°C.

Inject subcutaneously into the abdomen, thigh, or upper arm. Rotate injection sites weekly. Use a 29–31 gauge insulin syringe.

Side effects from the Phase 2 trial were predominantly gastrointestinal and dose-dependent:

• 1–2 mg: Mild nausea (12–16%), diarrhea (10–14%), generally well-tolerated.
• 4–8 mg: Nausea (20–28%), diarrhea (16–22%), decreased appetite, vomiting in 5–10%.
• 12 mg: Nausea (33%), diarrhea (25%), vomiting (11%). Most events were mild-to-moderate and occurred during dose escalation. Discontinuation due to GI events was 6%.

The glucagon receptor component may cause transient increases in heart rate (2–4 bpm on average). No clinically significant safety signals were identified in the Phase 2 data.

Retatrutide is an investigational compound currently in Phase 3 clinical trials. It is NOT FDA-approved and is not available for prescription or commercial purchase.

Like other GLP-1 agonists, retatrutide carries a theoretical risk of thyroid C-cell tumors (based on GLP-1 class effects in rodents), pancreatitis, and gallbladder events. The glucagon component adds unique considerations around hepatic effects and heart rate. Only participate in retatrutide research through authorized clinical trials.