Retatrutide Spray

Research Benefits

• Triple Receptor Agonism — Retatrutide is a first-in-class triple agonist targeting GIP, GLP-1, and glucagon receptors simultaneously, representing a new frontier in metabolic research.
• Superior Metabolic Effects — Published phase 2 studies demonstrated greater weight reduction compared to dual GIP/GLP-1 agonists, attributed to the additional glucagon receptor activity.
• Hepatic Fat Research — Glucagon receptor agonism promotes hepatic lipid oxidation, making retatrutide valuable for studying non-alcoholic fatty liver disease (NAFLD/NASH) pathways.
• Energy Expenditure — The glucagon component increases resting energy expenditure through hepatic thermogenesis, adding a metabolic output pathway to the incretin-mediated appetite suppression.

Mechanism of Action

Retatrutide (LY3437943) is a synthetic peptide that simultaneously activates three receptors involved in metabolic regulation: glucose-dependent insulinotropic polypeptide receptor (GIPR), glucagon-like peptide-1 receptor (GLP-1R), and glucagon receptor (GCGR).

GLP-1R Agonism: Enhances glucose-dependent insulin secretion, suppresses glucagon at high glucose, slows gastric emptying, and activates central satiety circuits in the hypothalamus and brainstem.

GIPR Agonism: Potentiates insulin secretion, enhances β-cell function, and may improve central weight regulation through hypothalamic GIP signaling. GIP agonism also enhances the GLP-1 response.

GCGR Agonism: Increases hepatic glucose output (counterbalanced by insulin effects), stimulates hepatic fatty acid oxidation and ketogenesis, and increases resting energy expenditure through mitochondrial uncoupling in the liver.

Synergistic Design: The three-receptor profile creates complementary metabolic effects: appetite suppression (GLP-1), metabolic efficiency (GIP), and energy expenditure (glucagon), with the insulin-stimulatory effects of GLP-1 and GIP counterbalancing glucagon's glycogenolytic action.

Research Protocol

Derived from published research. For research use only.

Reconstitution

Reconstitute in bacteriostatic water. Stock: 1-5 mg/mL.

Research Dosing (from published studies)

• In vivo (murine, metabolic): 1-30 nmol/kg SC, once daily or once weekly depending on acylation/half-life.
• Published phase 2 dose range (reference): 1-12 mg weekly SC in weight management studies, with dose escalation over 12-20 weeks.
• In vitro: 0.1-100 nM for receptor binding and cAMP assays.

Storage

Lyophilized at -20°C. Reconstituted at 2-8°C, use within 28 days.

Safety & Handling

Research Use Only.

Storage Conditions

• Lyophilized: -20°C
• Reconstituted: 2-8°C, 28 days

Known Considerations from Literature

• GI effects (nausea, vomiting, diarrhea) are common at higher doses, consistent with GLP-1R agonism.
• Glucagon component may transiently elevate blood glucose; monitor in diabetic models.
• Heart rate increases have been observed, warranting cardiovascular monitoring.
• Dose escalation protocols are recommended to mitigate GI adverse effects.

Handling

Standard PPE. Standard peptide handling procedures.

Frequently Asked Questions

What makes retatrutide a "triple agonist"?

Retatrutide simultaneously activates GIP, GLP-1, and glucagon receptors. Most incretin-based compounds are single (GLP-1) or dual (GIP/GLP-1) agonists. The addition of glucagon receptor agonism is what distinguishes retatrutide as a triple agonist.

How does the glucagon component help?

Glucagon receptor agonism increases hepatic fatty acid oxidation and resting energy expenditure, addressing the metabolic output side. GLP-1 primarily reduces input (appetite/absorption), so the combination addresses both sides of energy balance.

Why is dose escalation important?

GLP-1R agonists cause dose-dependent GI effects (nausea, vomiting). Gradual dose escalation allows receptor desensitization and tolerance development, reducing adverse events while achieving target doses.

What purity is this product?

BeaCapra Retatrutide is ≥99% pure by HPLC with full COA.