For research and educational purposes only. This page is a factual research reference, not medical advice. Any dosing figures shown are amounts reported in the research literature, provided for educational context — not instructions or recommendations for human use.
Overview
An investigational peptide developed by Eli Lilly as a single molecule targeting three receptors: GIP, GLP-1, and glucagon. It has been evaluated in clinical trials in the 2020s.
At a glance
ClassTriple GIP/GLP-1/glucagon receptor agonist
CategoryGLP-1 Family
SequenceTyr-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-alpha-Me-Leu-Leu-Asp-Lys-Lys-Ala-Gln-Aib-Ala-Phe-Ile-Glu-Tyr-Leu-Leu-Glu-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 (GIP-based backbone; Aib = 2-aminoisobutyric acid at positions 2 and 20, alpha-Me-Leu = alpha-methyl-L-leucine at position 13; Lys17 carries an AEEA plus gamma-Glu spacer to a C20 (eicosanedioic) fatty diacid; C-terminal amide)
Chain length39 amino acids
Molecular weight~4731 g/mol
Half-life~6 days
AliasesLY3437943
Page purposeResearch and educational reference
Regulatory statusInvestigational; not approved by the FDA or EMA. Under evaluation in clinical trials.
Selected evidence, in context
A closer reading of selected linked publications. This is not a systematic review, an evidence grade or a complete account of safety and effectiveness.
338 adults with obesity or overweight plus a weight-related condition; 48 weeks
Research question
How did body weight and adverse events vary across the tested retatrutide groups?
Reported finding
At 48 weeks, mean weight change ranged from −8.7% to −24.2% across active groups, versus −2.1% with placebo. Gastrointestinal events were common, and heart-rate increases were observed.
What this cannot establish
This phase 2 trial did not directly compare retatrutide with semaglutide or tirzepatide and cannot establish long-term or rare-event safety.
Retatrutide activates GIP, GLP-1 and glucagon receptors. The additional glucagon-receptor activity distinguishes its target profile from tirzepatide and semaglutide; receptor breadth alone does not establish a larger clinical benefit.
The cited 2023 phase 2 obesity trial enrolled 338 adults and compared retatrutide with placebo for 48 weeks. The highest active-treatment group had a mean body-weight change of -24.2%, compared with -2.1% for placebo. Gastrointestinal events and increases in heart rate were reported. The trial did not directly compare retatrutide with tirzepatide or semaglutide, so its result should not be described as proving superiority to either medicine.
The cited 2024 phase 2a liver-fat substudy reported reductions in measured liver fat in a selected group drawn from the obesity trial. These findings concern that study population and endpoint; they do not establish all liver-related outcomes. The cited phase 2 studies cannot by themselves establish long-term efficacy or rare-event safety.
Effects reported in research
The cited phase 2 obesity trial reported a mean body-weight change of -24.2% in its highest active-treatment group at 48 weeks, versus -2.1% with placebo.
Gastrointestinal adverse events and heart-rate increases were reported in that trial.
The cited phase 2a substudy reported liver-fat reductions in participants selected for elevated liver fat at baseline.
The cited obesity trial did not include semaglutide or tirzepatide as an active comparator; it does not establish superiority over either.
The cited studies do not establish long-term or rare-event safety.
Effects listed reflect findings reported in the research literature — many in animal or in-vitro models. Listing an effect is not a claim of efficacy or a therapeutic indication in humans.
Mechanism of action
Retatrutide is a synthetic peptide agonist designed to activate the GIP, GLP-1, and glucagon receptors simultaneously. GIP and GLP-1 agonism support glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, and appetite reduction, while glucagon-receptor agonism is proposed to increase energy expenditure. The combined activity is being studied for its effects on body weight and metabolic parameters.
Mechanistic description reflects published research-literature understanding. Much peptide research is preclinical (in-vitro or animal-model); mechanism in humans may differ and is not established for many compounds.
What it's studied for
Research contexts in which Retatrutide appears in the literature. Listing a research area is not a claim of efficacy or a therapeutic indication.
Body-weight regulation in clinical trialsGlycemic control in type-2-diabetes researchHepatic steatosis (MASH/NASH) endpoints under investigationMetabolic and energy-expenditure effects in early trials
Key characteristics
Investigational 'triple agonist' engineered to activate GIP, GLP-1, and glucagon receptors with one molecule
Adds glucagon-receptor agonism, which is hypothesized to raise energy expenditure alongside appetite suppression
Administered once weekly by subcutaneous injection in reported trials
Evaluated in mid-stage (Phase 2) and later clinical programs for obesity and type-2 diabetes
Receptor breadth describes the mechanism; it does not establish superiority over a single- or dual-receptor agonist
Reported research dosing reference only
Educational reference, not dosing guidance. The figures below summarize amounts reported in published research and research-community protocols, provided for educational and research context only. They are not medical advice, not a recommendation, and not instructions for human use. Retatrutide is a research compound.
The cited phase 2 obesity trial compared multiple retatrutide groups with placebo using study-specific regimens. Its protocol does not establish a general regimen for research-market material.
Reported frequencyOnce weekly (subcutaneous in the reported protocols)
ReconstitutionLyophilized powder typically reconstituted with bacteriostatic water; refrigerate and protect from light after reconstitution.
The cited phase 2 trial reported gastrointestinal adverse events and heart-rate increases. These data do not establish long-term or rare-event safety or a regimen for unsupervised use.
How it compares
Retatrutide differs from tirzepatide and semaglutide by adding a third target, the glucagon receptor, making it a triple agonist rather than a single or dual agonist.
Commonly studied alongside
Compounds frequently researched together with Retatrutide in the literature. Cross-referenced for research context — not a usage or combination recommendation.
Side-by-side pages for the pairings the literature already documents for Retatrutide, plus the unit-conversion reference for a reconstituted vial. Factual comparisons of documented characteristics — not a recommendation to combine or use any compound.
Retatrutide reconstitution calculator → Concentration, volume per measured amount and syringe units for a stated vial mass and diluent volume. A unit-conversion reference, not a dosing recommendation.
Handling & Stability
Lyophilized peptides are stored cold, protected from light, and reconstituted only at the time of intended in-vitro work.
Avoid repeated freeze-thaw cycles
Verify supplier lot and Certificate of Analysis
Follow institutional lab-safety protocols
Analytical & COA Concepts
Reputable research suppliers publish a third-party Certificate of Analysis per batch. Key analytical concepts referenced in COAs include:
What is retatrutide and what makes it a 'triple agonist'?
Retatrutide (LY3437943) is a single-molecule triple agonist that activates the GLP-1, GIP, and glucagon receptors. The added glucagon-receptor activity — associated in research with increased energy expenditure — is what distinguishes it from GLP-1 mono-agonists and GLP-1/GIP dual agonists. It is studied in models of obesity and metabolic regulation.
What is retatrutide's half-life and how does it shape study design?
A half-life of approximately six days has been reported for retatrutide, and the cited obesity trial used once-weekly administration. A pharmacokinetic value does not establish a safe regimen for an individual or validate research-market material.
What did the cited retatrutide phase 2 obesity trial compare?
The trial compared several retatrutide groups with placebo over 48 weeks (PMID 37366315). Gastrointestinal adverse events were common, and heart-rate increases were observed. It did not directly compare retatrutide with semaglutide or tirzepatide. Trial regimens are study-specific and do not provide instructions for using research material.
How does retatrutide differ from tirzepatide?
Tirzepatide targets GIP and GLP-1 receptors, while retatrutide also targets the glucagon receptor. The cited retatrutide phase 2 obesity trial used placebo as its comparator, not tirzepatide. Weight-change percentages from separate trials cannot establish which compound is more effective because the populations, designs and follow-up differ.
How should the investigational status in the cited studies be read?
Retatrutide was an investigational treatment in the cited phase 2 studies. Publication of a trial does not itself establish regulatory approval or authorize the use of material sold for research. Current approval information must be checked with the relevant regulator rather than inferred from a study phase.
What documentation should be expected for research-grade retatrutide?
Because it is a complex acylated peptide, a third-party COA with HPLC purity (commonly greater than or equal to 98%) and mass-spec identity confirmation is the standard reference to expect. Lyophilized material is stored cold and reconstituted with bacteriostatic water for research handling; freeze-thaw cycles and light exposure are avoided.
Publications indexed in PubMed and linked to this profile, including original studies and reviews. Publication labels reflect PubMed indexing, not evidence strength. Listing a study records that it exists and is indexed — it is not a claim of efficacy, a therapeutic indication, or an endorsement of its conclusions. Much of this literature is preclinical (in-vitro or animal-model).
Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial N Engl J Med, 2023. PubMed 37366315
Bibliographic metadata refreshed from PubMed on 2026-09-20. This checks the record identity and metadata; it is not a new review of every scientific claim. A reference may concern a related molecule or formulation: read its methods and the context above. See the editorial policy.
