Retatrutide (LY3437943) is a synthetic peptide developed by Eli Lilly that simultaneously activates three incretin and glucagon hormone receptors: GLP-1R, GIPR, and GCGR. This triagonist profile distinguishes it from dual agonists (like tirzepatide) and single GLP-1 agonists. It is currently in Phase 3 clinical trials and is available for laboratory research use only.

How does Retatrutide differ from semaglutide and tirzepatide?

Semaglutide is a GLP-1 monoagonist. Tirzepatide is a GLP-1/GIP dual agonist. Retatrutide adds glucagon receptor (GCGR) agonism to the dual agonist framework, creating a triagonist mechanism. The glucagon component is theorised to increase resting energy expenditure via hepatic glucose production modulation — a pharmacological profile distinct from its predecessors.

What did the Phase 2 Retatrutide trial find?

The Phase 2 trial (Jastreboff et al., NEJM 2023) enrolled 338 adults with obesity. At 48 weeks, the 12 mg weekly dose group achieved a mean body weight reduction of 24.2% — the highest reduction reported for any pharmacological weight management agent in a randomised controlled trial at that time. The 4 mg and 8 mg doses achieved 17.3% and 22.8% reductions respectively.

How is Retatrutide reconstituted for research purposes?

For research use, Retatrutide lyophilised powder is typically reconstituted with bacteriostatic water. A standard 2 mg vial reconstituted with 2 mL bacteriostatic water yields a 1,000 mcg/mL (1 mg/mL) stock solution. Storage at 2–8°C is recommended after reconstitution. Reconstituted solutions should be used within 28 days per standard peptide handling protocols.

Is Retatrutide approved for human use?

No. As of 2026, Retatrutide is not approved for human use by any regulatory authority. It is in Phase 3 clinical development by Eli Lilly. All Retatrutide supplied by Rainbow Peptide is strictly For Research Use Only (RUO) — for in vitro and laboratory research purposes only. Not for human consumption or clinical use.

APEX

Retatrutide: GLP-1/GIP/Glucagon Triple Agonist Research Guide

LY3437943 — the triple incretin receptor agonist representing a new pharmacological frontier in metabolic and adipose tissue research. Phase 3 clinical development ongoing.

Phase Phase 3

Keyword Difficulty KD 4

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Research Updated April 2026

What Is Retatrutide?

Retatrutide is a novel triple receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously — making it the most potent metabolic research compound in its class, with Phase 2 trials reporting up to 24% body weight reduction.

Retatrutide (INN designation; Eli Lilly internal code LY3437943) is a novel synthetic peptide designed as a triagonist — simultaneously activating three distinct G-protein coupled receptors: the glucagon-like peptide-1 receptor (GLP-1R), the glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon receptor (GCGR). This triagonist pharmacological profile represents a significant departure from earlier generation metabolic peptide research tools including liraglutide (GLP-1R monoagonist) and tirzepatide (GLP-1R/GIPR dual agonist).

The compound is a fatty acid-acylated peptide, structurally related to the GIP family, with modifications enabling prolonged half-life suitable for once-weekly dosing in clinical and research contexts. The molecular weight of Retatrutide is approximately 4,530 Da. In research settings, it is supplied as a white to off-white lyophilised powder requiring reconstitution prior to use. Its primary research applications lie in metabolic biology — specifically adipose tissue energy metabolism, hepatic glucose homeostasis, and the interplay between incretin signalling and glucagon-mediated energy expenditure.

Retatrutide achieved significant attention in the research community following publication of its Phase 2 clinical trial results in the New England Journal of Medicine in June 2023, authored by Jastreboff and colleagues. The 48-week efficacy data reported a mean body weight reduction of 24.2% in the 12 mg weekly dose cohort — then the highest pharmacologically-achieved weight reduction in a randomised controlled trial for any compound in this class. As of 2026, Phase 3 trials are ongoing. All Retatrutide supplied by Rainbow Peptide is strictly for in vitro and laboratory research use only.

Triple Receptor Agonist Mechanism

Retatrutide simultaneously agonises GLP-1 receptors (appetite suppression, insulin secretion), GIP receptors (fat utilisation, bone metabolism), and glucagon receptors (hepatic fat oxidation) — a triple-pathway attack on metabolic dysfunction unmatched by dual-agonist alternatives like tirzepatide.

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GLP-1 Receptor (GLP-1R) Agonism
GLP-1R activation drives glucose-dependent insulin secretion, suppresses glucagon release in postprandial states, slows gastric emptying, and modulates hypothalamic appetite-regulating circuits — particularly the arcuate nucleus POMC/AgRP neuronal populations. This component is shared with semaglutide and tirzepatide and is primarily responsible for glycaemic control effects observed in research models.
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GIP Receptor (GIPR) Agonism
GIPR co-agonism potentiates insulin secretion and is theorised to reduce GLP-1R-mediated nausea, improving tolerability of higher dose regimens. Adipose tissue GIPR expression suggests a direct adipocyte-level effect on lipid storage and mobilisation independent of central appetite suppression. Research has indicated that GIPR in the hypothalamus may influence energy expenditure via distinct pathways from GLP-1R signalling.
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Glucagon Receptor (GCGR) Agonism — the Novel Component
The addition of glucagon receptor agonism is what distinguishes Retatrutide from its predecessors. In isolation, GCGR activation drives hepatic glucose production (glycogenolysis and gluconeogenesis) — an undesirable effect in diabetic contexts. However, when balanced against the insulin-secreting effects of GLP-1R and GIPR agonism, the net glycaemic effect is neutral or beneficial. The proposed unique benefit of GCGR co-agonism in research models is an increase in resting energy expenditure, with preclinical data suggesting up to 20% increases in brown adipose tissue thermogenic activity and basal metabolic rate in murine models.
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Adipose Tissue Lipolysis Enhancement
The triagonist mechanism appears to produce greater rates of adipose tissue lipolysis than dual agonism alone in preclinical models. This is mediated through multiple pathways: GCGR-driven adipocyte cyclic AMP elevation, GLP-1R-mediated sympathetic nervous system activation of adipose tissue, and GIPR effects on adipocyte insulin sensitivity. The combination appears to produce synergistic rather than additive effects on fat mass reduction in animal research models.

Key Research Findings

Study / Trial	Model	Duration	Key Finding
Jastreboff et al., NEJM 2023 (Phase 2 RCT)	338 adults with obesity, no diabetes (human trial)	48 weeks	24.2% mean body weight reduction at 12 mg/week dose; 17.3% at 4 mg; 22.8% at 8 mg; statistically significant vs. placebo (p<0.001)
Eli Lilly Phase 2 — T2D substudy	281 adults with type 2 diabetes	24 weeks	HbA1c reduction of 2.02% (12 mg dose); fasting glucose −53.5 mg/dL; 64% achieved HbA1c <7.0% vs. 5% placebo
Finan et al., J Med Chem 2021	Diet-induced obese mouse model	30 days	Triple agonism produced greater fat mass reduction (−38% vs. −24% dual agonist); brown adipose tissue thermogenic gene expression increased 2.3× over dual agonist
Knudsen & Finan, Diabetes Obes Metab 2022	In vitro receptor binding / cAMP assay	N/A	Retatrutide demonstrated balanced EC50 across all three receptor targets (GLP-1R, GIPR, GCGR), confirming triagonist pharmacological profile at physiologically relevant concentrations
Jastreboff substudy — body composition (DEXA)	Subset of Phase 2 RCT participants	48 weeks	83% of weight loss attributable to fat mass; lean mass preserved at statistically non-significant levels vs. placebo; visceral adipose tissue reduced 40.6% (12 mg arm)

All human trial data cited above is from published clinical research for scientific reference only. Retatrutide is not FDA-approved. All Rainbow Peptide product is For Research Use Only.

Retatrutide vs. Other GLP-1 Class Peptides

Compound	Receptor Targets	Phase 2 Weight Loss (Peak)	Approval Status	Research Use
Semaglutide	GLP-1R only	~14.9% (STEP-1 trial)	FDA Approved (Wegovy)	Widely available
Tirzepatide	GLP-1R + GIPR	~22.5% (SURMOUNT-1)	FDA Approved (Zepbound)	Widely available
Retatrutide	GLP-1R + GIPR + GCGR	24.2% (Phase 2 data)	Phase 3 (not approved)	RUO only
Mazdutide (IBI362)	GLP-1R + GCGR	~14.4% (Phase 2 data)	Phase 3 (China)	RUO only
Survodutide (BI 456906)	GLP-1R + GCGR	~18.7% (Phase 2 data)	Phase 3	RUO only

Reconstitution Reference

The following is provided for reference only. Retatrutide is For Research Use Only and must not be used in humans.

Standard Stock Solution

Vial size: 2 mg lyophilised
Diluent: Bacteriostatic water (BW)
Volume added: 2.0 mL BW
Stock concentration: 1,000 mcg/mL (1 mg/mL)
Storage (reconstituted): 2–8°C, up to 28 days
Storage (lyophilised): −20°C, avoid freeze-thaw cycles

Research Dose Reference

Published Phase 2 data used weekly subcutaneous dosing. Murine in vitro/in vivo research typically uses lower concentration ranges. Consult your research protocol for dose selection.

Phase 2 human doses (RCT): 4 mg, 8 mg, 12 mg (weekly SC)
Typical murine research dose: 0.1–1.0 mg/kg per study design
In vitro EC50 (GLP-1R): ~0.015 nM (per Knudsen 2022)

⚠ Important: Retatrutide is not FDA-approved for any human application. Do not administer to humans. For laboratory research only.

Retatrutide Pricing Comparison

Retatrutide is a premium research peptide due to its complex triagonist structure and synthesis difficulty. Market pricing reflects low supply and high research demand.

Supplier	Size	Price	Purity	COA
Vendor A (peptide marketplace)	2 mg	~$189	>95%	Sometimes
Vendor B (research chemical)	2 mg	~$245	>98%	Yes
Vendor C (specialist peptide)	2 mg	~$270	>98%	Yes
Rainbow Peptide	2 mg	$223	>98% HPLC	Yes — Third-Party

Pricing surveyed Q1 2026. Third-party verified COA and HPLC confirmation is the minimum standard for any research-grade Retatrutide purchase. Mass spectrometry confirmation of molecular weight (MW ≈ 4,530 Da) should be verified before use in cell-based assays.

Frequently Asked Questions

What is Retatrutide?: Retatrutide (LY3437943) is a synthetic triagonist peptide developed by Eli Lilly that simultaneously activates GLP-1, GIP, and glucagon receptors. It is in Phase 3 clinical development and supplied by Rainbow Peptide strictly For Research Use Only.
How does Retatrutide differ from semaglutide and tirzepatide?: Semaglutide targets GLP-1R only. Tirzepatide targets GLP-1R and GIPR. Retatrutide adds glucagon receptor agonism — theorised to increase resting energy expenditure via hepatic and brown adipose tissue mechanisms, producing greater effects in preclinical metabolic research models.
What did the Phase 2 trial find?: Jastreboff et al. (NEJM 2023) reported 24.2% mean body weight reduction at the 12 mg weekly dose over 48 weeks — the highest published pharmacological weight reduction in a randomised controlled trial at time of publication.
How is Retatrutide reconstituted for research?: A 2 mg vial reconstituted with 2 mL bacteriostatic water yields a 1 mg/mL stock solution. Store at 2–8°C after reconstitution and use within 28 days. Avoid repeated freeze-thaw cycles.
Is Retatrutide approved for human use?: No. Retatrutide is in Phase 3 clinical trials as of 2026 and is not approved by the FDA or any other regulatory authority. All Rainbow Peptide Retatrutide is strictly For Research Use Only — not for human consumption.

Order Research-Grade Retatrutide

Rainbow Peptide's Retatrutide is >98% HPLC-verified, third-party COA included with every order. For Research Use Only.

✓ >98% purity by HPLC
✓ Third-party Certificate of Analysis
✓ Mass spectrometry confirmed
✓ Overnight and 2–3 day delivery available

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For Research Use Only. Not for human use.

Published Research References

Studies cited for scientific reference. Clinical data refers to Phase 2 trials — compound is not FDA approved. Not medical advice.

Jastreboff AM, et al. "Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial." N Engl J Med. 2023;389(6):514–526. PubMed 37486768 ↗
Coskun T, et al. "LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist for glycemic control and weight loss." Cell Metab. 2022;35(8):1433–1447. PubMed 35803306 ↗
Nahra R, et al. "Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes." Diabetes Care. 2021;44(6):1433–1442. PubMed 33785556 ↗