Retatrutide

Retatrutide | LY3437943 | GIP/GLP-1/Glucagon Triple Receptor Agonist | Research Peptide

Also Known As: LY3437943 Mechanism: Triple agonist — GIP, GLP-1, and glucagon receptor Molecular Structure: 39-amino acid peptide with C20 fatty diacid moiety Purity: >99% (HPLC verified) Form: Lyophilised powder Available Sizes: 5mg | 10mg Storage: –20°C, away from light and moisture CAS Number: 2381089-83-2

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What Is Retatrutide?

Retatrutide (developmental code: LY3437943) is an investigational synthetic peptide developed by Eli Lilly and Company. It is a first-in-class triple hormone receptor agonist, designed as a single molecule that simultaneously activates three distinct receptors: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon (GCG). This multi-receptor mechanism distinguishes retatrutide from earlier generations of incretin-based research compounds — including GLP-1 mono-agonists such as semaglutide, and dual GIP/GLP-1 agonists such as tirzepatide — by introducing glucagon receptor activation as an additional metabolic axis.

Structurally, retatrutide is a 39-amino acid peptide conjugated to a C20 fatty diacid moiety, which confers an extended pharmacokinetic half-life suitable for once-weekly dosing in clinical research settings. Compared to endogenous GLP-1 and glucagon, retatrutide demonstrates lower potency at GLP-1 and glucagon receptors but substantially higher potency at the human GIP receptor — a pharmacological profile deliberately engineered to balance efficacy with tolerability.

Retatrutide has progressed through Phase 2 clinical trials and into the Phase 3 TRIUMPH programme — one of the most significant and closely watched clinical development programmes in metabolic research. It currently represents the most clinically advanced triple hormone receptor agonist in the scientific literature and is among the most actively researched peptides in the field of metabolic and obesity science.

Our retatrutide is supplied for research purposes only, synthesised under strict quality-controlled manufacturing conditions and verified to a purity of greater than 99% by High-Performance Liquid Chromatography (HPLC) and Mass Spectrometry (MS). It is provided as a lyophilised (freeze-dried) powder for maximum stability.

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Research Background & Clinical Trial Data

Retatrutide has one of the most substantive and rapidly evolving clinical research profiles of any peptide currently available for laboratory study. The compound has been evaluated in multiple randomised, placebo-controlled trials and has generated results that have been published in leading peer-reviewed journals including the New England Journal of Medicine, The Lancet, and Nature Medicine.

Triple Receptor Mechanism of Action Retatrutide's triple agonist mechanism operates across three complementary metabolic pathways. GLP-1 receptor activation suppresses appetite, slows gastric emptying, and promotes insulin secretion in a glucose-dependent manner. GIP receptor activation enhances insulin secretion, modulates adipose tissue metabolism, and appears to synergise with GLP-1 activity to produce greater metabolic effects than either hormone alone — as demonstrated by the clinical performance of the dual agonist tirzepatide. The addition of glucagon receptor agonism introduces a third axis: increased energy expenditure, enhanced hepatic fat oxidation, and PCSK9-mediated reduction in LDL cholesterol. The net result of this triple activation is a broader and potentially more powerful metabolic response than earlier generation single or dual receptor agonists.

Phase 2 Obesity Trial — New England Journal of Medicine (2023) The pivotal Phase 2 obesity trial of retatrutide, published in the New England Journal of Medicine, enrolled 338 adults with obesity (BMI ≥30) or overweight with weight-related comorbidities. Participants received once-weekly subcutaneous retatrutide at doses of 1 mg, 4 mg, 8 mg, or 12 mg, or placebo, for 48 weeks. The results were notable even by the elevated standards of the modern incretin era. At 48 weeks, participants on the 8 mg dose achieved a mean body weight reduction of 22.8%, while those on the highest 12 mg dose achieved a mean reduction of 24.2% — compared to just 2.1% in the placebo group. Notably, 100% of participants in both the 8 mg and 12 mg groups achieved at least 5% body weight reduction, with 83% of the 12 mg group achieving reductions of 15% or more. These findings were accompanied by meaningful improvements in cardiometabolic markers including waist circumference, blood pressure, fasting glucose, HbA1c, insulin levels, and lipid profiles.

Phase 2 Type 2 Diabetes Trial — The Lancet (2023) A parallel Phase 2 trial published in The Lancet assessed retatrutide in 281 participants with type 2 diabetes over 36 weeks. At the highest dose of 12 mg, participants achieved mean body weight reduction of 16.9% compared to 3.0% with placebo. Glycaemic outcomes were equally striking: 77–82% of participants on retatrutide achieved euglycaemia (HbA1c ≤6.5%), and between 57–63% achieved body weight reductions of 15% or more. These results were described by lead investigators as the most significant weight loss outcomes reported in a clinical trial for type 2 diabetes at that time.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD/NASH) — Nature Medicine (2024) A substudy of the Phase 2 obesity trial, published in Nature Medicine, examined retatrutide's effects in participants with metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD). Results demonstrated substantial reductions in liver fat content at 24 weeks across all active doses, with the 8 mg and 12 mg doses producing mean relative liver fat reductions of 81.4% and 82.4% respectively, compared to a +0.3% change with placebo. At the highest doses, more than 90% of participants achieved normalisation of liver fat — findings of significant interest to researchers working in hepatology and fatty liver disease.

Phase 3 TRIUMPH Programme Retatrutide has now entered the Phase 3 TRIUMPH clinical programme, one of the most expansive trial programmes currently underway in obesity and metabolic medicine. The TRIUMPH programme is evaluating retatrutide across multiple indications including chronic weight management, type 2 diabetes, knee osteoarthritis, moderate-to-severe obstructive sleep apnoea, chronic low back pain, cardiovascular and renal outcomes, and MASLD. In December 2025, Eli Lilly announced positive topline results from TRIUMPH-4 — a 68-week Phase 3 trial in adults with obesity and knee osteoarthritis — in which retatrutide delivered average weight loss of up to 71.2 lbs alongside substantial reductions in osteoarthritis pain. Phase 3 trials across the broader TRIUMPH programme are projected to continue through 2025 and beyond, with regulatory submission timelines dependent on full data readouts.

Cardiometabolic Research Beyond weight reduction, retatrutide's glucagon receptor component has attracted research interest for its cardiovascular effects. Phase 2 data demonstrated LDL cholesterol reductions of approximately 20%, a finding researchers have attributed to glucagon agonism-mediated effects on PCSK9 degradation. Reductions in systolic and diastolic blood pressure, triglycerides, and markers of insulin resistance have also been observed, positioning retatrutide as a subject of broad interest across cardiometabolic research.

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Product Specifications

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Quality & Purity Assurance

Every batch of our retatrutide undergoes a rigorous multi-stage quality control process before release to researchers. Our assurance pipeline includes:

• HPLC Analysis — confirms peptide purity exceeding 99%
• Mass Spectrometry (MS) — verifies molecular identity, fatty acid conjugation integrity, and sequence accuracy
• Endotoxin Testing — ensures the product is free from bacterial endotoxins
• Certificate of Analysis (CoA) — available for every batch upon request

Full batch traceability is maintained across synthesis, purification, and quality testing, giving researchers the confidence required for reproducible, high-quality experimental work.

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Handling & Reconstitution (Research Use)

Retatrutide lyophilised powder should be reconstituted using sterile bacteriostatic water or phosphate-buffered saline (PBS). Gently swirl the vial — do not vortex. Once reconstituted, aliquot immediately and store at –20°C. As with all peptide conjugates containing fatty acid moieties, repeated freeze-thaw cycles should be strictly avoided to preserve the structural integrity of the molecule and the reliability of experimental results.

All handling should comply with standard laboratory safety protocols and applicable institutional or regulatory guidelines.

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Retatrutide in Context: How It Compares to Other Research Peptides

Retatrutide occupies a distinct position within the broader research peptide landscape. Unlike tissue-focused peptides such as BPC-157 and TB-500, or genomic and matrix-remodelling peptides such as GHK-Cu, retatrutide operates as a hormonal receptor agonist targeting the systemic neuroendocrine regulation of metabolism. Its triple receptor mechanism sets it apart even from other incretin-class research compounds — representing the next evolutionary step beyond semaglutide (GLP-1 mono-agonist) and tirzepatide (GLP-1/GIP dual agonist) in the hierarchy of metabolic peptide research.

For researchers building a comprehensive metabolic peptide panel, retatrutide complements MOTS-c — which operates at the mitochondrial and intracellular metabolic level — by providing a systemic hormonal signalling perspective on energy homeostasis and metabolic regulation.

All peptides in our catalogue are manufactured to the same >99% purity standard and are supported by batch-specific Certificates of Analysis.

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Important Notice

This product is intended strictly for in vitro research and laboratory use only. Retatrutide is an investigational compound and is not approved for human or veterinary use by the FDA, EMA, or any other regulatory authority. It is not a drug, supplement, or food product. This product must not be administered to humans or animals. By purchasing this product, the buyer confirms they are a qualified researcher and will use the compound solely for lawful scientific research purposes.