Retatrutide

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What Is Retatrutide

Retatrutide (investigational designation LY3437943) is a synthetic 39-amino-acid peptide developed by Eli Lilly as the first clinical-stage triple agonist of the GLP-1, GIP, and glucagon receptors. Where earlier incretin peptides act on one receptor (semaglutide — GLP-1) or two (tirzepatide — GLP-1 plus GIP), retatrutide engages all three metabolic receptors simultaneously. This distinct pharmacology is being studied for obesity, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD/MASH), and hypertension-linked metabolic syndrome.

The peptide has a molecular weight of approximately 4,731.4 Da, empirical formula C₂₂₁H₃₄₂N₄₆O₆₈, and is supplied as a high-purity lyophilized powder for reconstitution with bacteriostatic water. It is for laboratory research use only and is not intended for human or veterinary diagnosis or therapy. For deeper mechanism, trial, and outlook detail, see our full Retatrutide research guide.

Mechanism of Action — GLP-1/GIP/Glucagon Triple Agonist

Retatrutide’s receptor profile is what differentiates it from every other metabolic peptide currently on the market or in late-stage trials. Each of the three receptors contributes a distinct pathway to the observed effects on body composition, glucose control, and energy balance:

• GLP-1 receptor — the same receptor activated by semaglutide (Ozempic, Wegovy) and liraglutide. Agonism slows gastric emptying, enhances satiety signaling in the hypothalamus, and stimulates glucose-dependent insulin secretion from pancreatic beta cells.
• GIP receptor — the second pathway added by tirzepatide (Mounjaro, Zepbound). GIP agonism improves insulin sensitivity in adipose tissue, blunts the nausea ceiling of GLP-1 alone, and supports adipocyte lipid-handling efficiency.
• Glucagon receptor — the novel third pathway unique to retatrutide. Glucagon agonism increases basal energy expenditure, promotes hepatic lipid oxidation, and reduces liver fat — effects the GLP-1/GIP duo does not reproduce.

Because increased energy expenditure via glucagon stacks additively on top of the appetite suppression driven by GLP-1/GIP, retatrutide produces both a larger energy deficit and a more favourable body-composition profile in preclinical models than dual-agonist peptides. In phase 2 research data, fat-mass loss accounted for the majority of total weight reduction, with preserved lean mass in the higher dose arms.

Published Trial Data

The headline retatrutide dataset is the phase 2 obesity trial published by Jastreboff and colleagues in the New England Journal of Medicine in June 2023 (n = 338 participants with obesity, 48-week treatment period). At the highest tested dose of 12 mg weekly, participants experienced a mean body-weight reduction of 24.2% from baseline. The comparator semaglutide arm in the STEP-1 trial produced 14.9% reduction at 68 weeks and the tirzepatide arm in SURMOUNT-1 produced 22.5% at 72 weeks — so retatrutide achieved a numerically larger reduction in a shorter treatment window. Head-to-head comparative trials have not yet been published.

A parallel phase 2 diabetes programme (Rosenstock et al., Lancet 2023) demonstrated HbA1c reductions of up to 2.16 percentage points at 36 weeks in participants with type 2 diabetes, again at the 12 mg weekly dose. A phase 2 NAFLD sub-study reported a 51.3% relative reduction in liver-fat content after 24 weeks at the 8 mg dose — the largest liver-fat reduction reported for any incretin-class peptide to date.

Eli Lilly is currently running the TRIUMPH phase 3 programme, including TRIUMPH-1 (obesity), TRIUMPH-2 (obesity with type 2 diabetes), TRIUMPH-3 (obesity with cardiovascular disease), and TRIUMPH-4 (sleep apnea plus obesity). Phase 3 readouts are expected to inform eventual regulatory submission.

Research Applications

Retatrutide is used in laboratory research contexts that investigate:

• Obesity and body-weight regulation — mechanistic work on appetite signaling, gastric emptying kinetics, and energy expenditure in rodent and in-vitro models
• Insulin sensitivity and glucose homeostasis — effects on insulin secretion, hepatic glucose output, and peripheral glucose disposal
• Hepatic steatosis / MASH — liver fat mobilisation and transaminase response in fatty-liver research models
• Receptor pharmacology — comparative binding, selectivity, and downstream signaling studies across the GLP-1/GIP/glucagon receptor triad
• Comparative metabolic-peptide research — benchmarking against tirzepatide (dual GLP-1/GIP agonist) and other investigational compounds for potency, tolerability, and body-composition outcomes. See our tirzepatide vs semaglutide comparison for the dual-agonist baseline.
• Healing and recovery peptide stacking — research protocols that pair metabolic peptides with repair compounds such as BPC-157 in preclinical studies.

For broader context on where retatrutide fits within the weight-loss peptide landscape, see our peptide stacks for fat loss research guide and the overall GLP-1 weight-loss injections guide. Browse the complete research peptides catalog for related compounds.

Available Strengths and Concentrations

MedsBase stocks retatrutide in the following lyophilized vial sizes. Each variation is supplied in 10-vial and 20-vial pack formats, shipped under chilled conditions with reconstitution instructions:

All strengths are supplied in the same chemical form (lyophilized powder, 99%+ HPLC purity). Higher-mg vials offer lower per-mg cost but require smaller reconstitution volumes to maintain standard U-100 syringe concentrations — see the dilution chart below.

How It Compares — Retatrutide vs Tirzepatide vs Semaglutide

The following summary is based on published trial data. Retatrutide is still in phase 3 development and the comparisons below are across separate studies, not head-to-head.

For a deeper comparison of tirzepatide versus semaglutide specifically, see Tirzepatide vs Semaglutide: Weight Loss, Dosing & Cost.

Storage and Reconstitution

Before reconstitution: store lyophilized vials refrigerated at 2–8 °C in the original foil packaging. Under these conditions, lyophilized retatrutide remains stable for up to 36 months. Avoid repeated temperature cycling.

Reconstitution procedure: add bacteriostatic water to the peptide vial per the dilution table above. Inject the water down the side wall of the vial rather than directly onto the lyophilized cake. Swirl gently — do δεν shake — and allow 5–10 minutes for complete dissolution. A fully reconstituted solution should be clear and colourless.

After reconstitution: store the solution refrigerated at 2–8 °C and use within 30 days for optimal stability. Do not freeze the reconstituted solution — freeze-thaw cycles degrade peptide integrity. Discard any vial showing cloudiness, precipitate, or discolouration.

Συχνές Ερωτήσεις

What is retatrutide used for in research?

Retatrutide is used in laboratory research investigating obesity, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD/MASH), insulin sensitivity, appetite regulation, and comparative metabolic-peptide pharmacology. It is δεν approved by the FDA, EMA, or other regulators for human therapeutic use and is sold here strictly for laboratory research use only.

How is retatrutide different from tirzepatide and semaglutide?

Retatrutide is the first triple receptor agonist, binding GLP-1, GIP, και glucagon receptors in one molecule. Tirzepatide binds GLP-1 and GIP (dual). Semaglutide binds only GLP-1 (single). The added glucagon pathway in retatrutide increases energy expenditure and reduces liver fat in ways dual and single agonists do not reproduce.

How much weight loss has retatrutide shown in trials?

The phase 2 obesity trial published by Jastreboff et al. in NEJM (2023) reported a mean body-weight reduction of 24.2% at 48 weeks at the highest tested dose of 12 mg weekly. For context, tirzepatide’s phase 3 highest-dose arm produced 22.5% at 72 weeks and semaglutide’s produced 14.9% at 68 weeks. Phase 3 retatrutide results from the TRIUMPH programme are pending.

Is retatrutide FDA approved?

No. Retatrutide is currently in phase 3 clinical development under Eli Lilly’s TRIUMPH programme and has not received regulatory approval from the FDA, EMA, MHRA, or any other authority. The peptide sold by research-use-only suppliers is for laboratory investigation, not for human therapeutic use.

What strengths does MedsBase stock?

MedsBase carries retatrutide in 5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 50 mg, and 60 mg lyophilized vials. Each strength is available in 10-vial or 20-vial pack sizes. All vials are supplied at 99%+ HPLC purity with a certificate of analysis on request.

How do I reconstitute retatrutide?

Follow the dilution chart above. A 10 mg vial with 2.0 mL of bacteriostatic water yields 5.0 mg/mL, so 40 ticks on a U-100 (1 mL / 100-unit) insulin syringe equals 2 mg. Inject BAC water down the side wall, swirl gently (do not shake), and allow 5–10 minutes for dissolution before use.

How should retatrutide be stored?

Lyophilized vials: refrigerated at 2–8 °C in original packaging, stable up to 36 months. Reconstituted solution: refrigerated at 2–8 °C, use within 30 days. Do not freeze reconstituted solution — freeze-thaw cycles degrade the peptide.

What is the typical research dose of retatrutide in studies?

Phase 2 obesity-trial arms tested 1 mg, 4 mg, 8 mg, and 12 mg weekly doses over 48 weeks. Weight-loss response was dose-dependent, with 24.2% reduction observed at the 12 mg arm. Laboratory research protocols typically mirror these trial doses when the intent is to model published efficacy data.

Does retatrutide cause the same side effects as other GLP-1 peptides?

In published trials, the most common treatment-emergent events were dose-dependent gastrointestinal effects — nausea, diarrhoea, constipation — similar in profile to semaglutide and tirzepatide. The added glucagon receptor activity has not produced unexpected safety signals in phase 2, but the full tolerability profile awaits phase 3 readouts.

How long until retatrutide is FDA approved?

Eli Lilly’s TRIUMPH phase 3 programme enrolled starting in 2023–2024 with primary completion dates projected for 2025–2027 depending on sub-trial. Assuming positive readouts, an FDA submission could follow 12–18 months after primary completion. Regulatory approval timelines are speculative until Lilly announces filing.

What is the half-life of Retatrutide?

Retatrutide (LY3437943) has a long elimination half-life of approximately 6 days in Phase I clinical data, attributed to the C18 fatty acid modification that enables albumin binding. This extended half-life supports once-weekly dosing schedules used in clinical trials.

How does Retatrutide compare to Tirzepatide and Semaglutide?

Retatrutide is a triple agonist (GLP-1 / GIP / Glucagon receptors), compared to Tirzepatide’s dual agonism (GLP-1 / GIP) and Semaglutide’s single GLP-1 agonism. Phase II clinical trial data for Retatrutide reported weight reduction of up to 24% at 48 weeks — exceeding outcomes for both Tirzepatide and Semaglutide at comparable timepoints. The additional glucagon receptor activity is believed to drive greater energy expenditure and fat oxidation.

Can I order retatrutide for international shipping?

Yes. MedsBase ships retatrutide worldwide from our dedicated peptide shipping network. Peptide-only orders qualify for our standalone peptide shipping service. Orders are shipped in temperature-controlled packaging with full tracking.

Other Peptides for Recovery and Performance Research

• BPC-157 — Body Protection Compound — tendon, ligament, gut recovery research
• TB-500 — Thymosin Beta-4 fragment — soft tissue and vascular recovery research
• Ιπαμορελίνη — Selective ghrelin agonist — clean GH pulse without cortisol/prolactin
• CJC-1295 with DAC — GHRH analog with extended half-life
• GHK-Cu — Copper peptide — skin and connective tissue regeneration research

Further Reading

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