Retatrutide
Investigational triple agonist (GLP-1 / GIP / glucagon) with the largest weight-loss effect of any compound yet reported in its class.
39 residues· First described 2022
Triple agonist: GIP/GLP-1/glucagon receptors. Aib at positions 2 and 13; C20 fatty diacid
Overview
Retatrutide is Eli Lilly's investigational "triple agonist" - a single molecule that activates the GIP, GLP-1, and glucagon receptors simultaneously. The addition of glucagon agonism is the distinctive feature, and appears to drive additional energy expenditure alongside the appetite-suppression and metabolic effects of the GIP/GLP-1 components. In Phase 2 data, retatrutide produced ~24% mean body weight reduction at 48 weeks at the highest dose - the largest effect reported to date for any pharmacologic weight-loss compound.
Retatrutide is currently in Phase 3 trials and is not FDA-approved. Most current usage in the community is from research chemical suppliers or gray-market sources, which raises quality and dosing accuracy concerns relative to FDA-approved semaglutide and tirzepatide. Users considering retatrutide should carefully evaluate source quality and work with a physician who can monitor both weight and the broader metabolic picture.
Beyond weight, early retatrutide data has shown favorable movement on metabolic markers - HbA1c, ApoB, triglycerides, hepatic steatosis markers. One watch item: retatrutide has produced modest heart-rate elevation (~4–6 bpm) in trials, which should be tracked in anyone with existing cardiovascular considerations.
Mechanism of Action
Retatrutide is a synthetic single-chain peptide that activates three receptors: GIP (insulinotropic, adipose tissue modulation), GLP-1 (insulin secretion, glucagon suppression, appetite reduction, gastric emptying), and glucagon (hepatic glucose output, energy expenditure). The glucagon agonism is what drives additional caloric burn beyond appetite reduction alone, effectively producing a "metabolic acceleration" layered on top of the appetite-suppression effects.
Community Usage Patterns
Research dosing in Phase 2 escalated 2 mg → 12 mg over 12 weeks. Most community protocols use a similar slow titration starting at 1–2 mg. No pharmacy-compounded version exists in the US; all current access is via research chemical channels. Tracking: weight, HbA1c, lipid panel (with ApoB), fasting glucose, heart rate, LFTs. Because of the glucagon component, hepatic markers (ALT, AST) deserve baseline and ongoing monitoring.
Education only - not medical advice. Any protocol change should involve your licensed provider.
Biomarkers to Track
When running Retatrutide, these are the biomarkers most commonly tracked to assess response and safety:
Reconstitution Calculator
Free calculator for Retatrutide reconstitution math - vial size, BAC water volume, and exact syringe units.
Open Retatrutide calculator →Related Reading
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Retatrutide Head-to-Head Comparisons
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