Retatrutide (LY3437943): physical form, storage and reconstitution in the lab

Physical form and specification

Retatrutide (LY3437943) is a single synthetic peptide of roughly 39 residues (molecular weight ~4731 Da) and a triple agonist of the GIP, GLP-1 and glucagon receptors, not a mono GLP-1 analogue. As a reagent it is supplied as a white to off-white lyophilized (freeze-dried) powder, ≥98–99% purity by HPLC, in sealed glass vials of 5, 10, 20 and 60 mg (the 5 mg vial is the reference specification). Several engineered handles define the molecule: α-aminoisobutyric acid (Aib) at positions 2 and 20, α-methyl-leucine at position 13, and a C20 fatty-diacid acylation on the lysine at position 17, which is what confers reversible albumin binding.

Reconstitution chemistry

The lyophilizate dissolves readily in aqueous buffer. Reconstitute directly in the vial with bacteriostatic water for injection (water with 0.9% benzyl alcohol); the benzyl alcohol limits microbial growth in a multi-draw vial. Introduce the diluent slowly down the vial wall rather than jetting it onto the powder cake: the C20 fatty-diacid tail makes the peptide surface-active and prone to foaming, and foam denatures peptide at the air–water interface. Swirl gently until clear; do not vortex or shake. Concentration is set by the diluent volume (mass in the vial ÷ mL added), e.g. 5 mg dissolved in 1 mL gives 5 mg/mL. If a preservative-free matrix is required, sterile water or a defined buffer can be substituted, at the cost of no bacteriostatic protection.

Storage and stability

Store the sealed lyophilized vial at 2–8 °C, protected from light; do not freeze. The dry powder is the stable form and tolerates brief temperature excursions in transit. Once reconstituted, retatrutide is a solution: keep it at 2–8 °C, protected from light, do not freeze, and use it within a few weeks. Discard any solution that turns cloudy or shows particulates. The extended terminal half-life of roughly 6 days, which supports once-weekly subcutaneous dosing in research models, comes from the C20 fatty-diacid at Lys17 binding reversibly to serum albumin; in solution the peptide remains susceptible to oxidation and aggregation, so prepare working dilutions close to the time of use.

Lab handling

Let a cold vial equilibrate to room temperature before opening to avoid condensation onto the powder. Where possible use low-protein-binding tips and tubes, since surface-active, lipidated peptides adsorb to plastic and glass and can quietly lower the working concentration. Record the lot number and reconstitution date on the vial.

Research context

Retatrutide is a reference triple-agonist (“triagonist”) scaffold acting at the GIP, GLP-1 and glucagon receptors simultaneously. It is used in vitro and in animal models to probe combined incretin- and glucagon-receptor signaling, receptor-bias and cAMP assays, energy-expenditure and metabolic studies, and comparative pharmacology against single- and dual-receptor agonists. The long half-life engineered through fatty-diacid albumin binding also makes it a model compound for studying lipidation-based half-life extension across a three-receptor pharmacology.