Fat LossWell-evidencedHuman trials

Retatrutide

Retatrutide

Overview

Retatrutide is a first-in-class triple agonist targeting GIP GLP-1 and glucagon receptors simultaneously developed by Eli Lilly. Phase 2 trial data published in 2023 showed average weight loss of 24% of body weight at 48 weeks — the highest weight loss ever reported for a pharmacological intervention in a clinical trial. Retatrutide represents the frontier of metabolic peptide therapeutics combining three complementary receptor agonist mechanisms for unprecedented efficacy in obesity treatment.

Mechanism of Action

Retatrutide simultaneously activates three receptors involved in energy metabolism. GLP-1 receptor agonism provides incretin effects appetite suppression and gastric emptying delay. GIP receptor agonism complements GLP-1 signaling in the pancreas and adipose tissue improving insulin sensitivity and lipid metabolism. Glucagon receptor agonism adds a third mechanism — stimulating hepatic fat burning and increasing energy expenditure through thermogenic effects. The glucagon component is particularly important for differentiating retatrutide from dual GIP/GLP-1 agonists like tirzepatide — glucagon receptor activation directly increases metabolic rate and fat oxidation producing weight loss through both reduced intake and increased expenditure. The combination of all three mechanisms produces the remarkable efficacy observed in trials.

Dosage Information

Typical Dose

1-12 mg weekly (Phase 2 trial doses)

Frequency

Once weekly

Anytime

Administration

Subcutaneous injection

Notes

Currently in Phase 3 clinical trials. Not yet FDA approved. This entry documents the research context for this highly anticipated compound.

Where does Retatrutide sit?

See how this peptide compares across all 111 peptides in our database.

Evidence Score

0.75

Clinical trials
1.0035%
Literature
0.9130%
Community
0.0020%
Completeness
0.8815%
2 RCTs1 clinical trials28 reviews

Compound Data

Retatrutide structure

Molecular Formula

C221H342N46O68

Molecular Weight

4731.00 g/mol

IUPAC Name

20-[[(1S)-4-[2-[2-[2-[[(5S)-5-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-5-amino-2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-methylpropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-2,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]hexanoyl]amino]-6-[[(2S)-1-[[(2S)-5-amino-1-[[1-[[(2S)-1-[[(2S)-1-[[(3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[2-[(2S)-2-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[(2S)-2-[(2S)-2-[(2S)-2-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-2-oxoethyl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-2-methyl-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-6-oxohexyl]amino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-20-oxoicosanoic acid

PubChem CID

171390338

Potential Side Effects

Nausea (very common)Vomiting (common)Diarrhea (common)Decreased appetite (pronounced)Gallbladder issues with rapid weight loss (uncommon)

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Quick Facts

Administration
Subcutaneous injection
Typical Dose
1-12 mg weekly (Phase 2 trial doses)
Frequency
Once weekly
References
0 curated + 43 from PubMed
Clinical Trials
32 registered
Evidence Score
0.8 / 100