Is there any published stability data for orforglipron at room temperature?

Concretely: orforglipron · room temperature.

This has the shape of a fact but I cannot find its origin.

What I found instead were three secondary sources all citing each other.

Has anyone verified this independently?

room temperature is one of the two points formal stability programmes actually run, so this is the rare case where the literature is looking where you are. Accelerated work is conventionally run at 25 °C and 40 °C, with the refrigerated condition as the control. Room temperature is not a number, so take the pharmacopoeial 20–25 °C and its 22.5 °C midpoint: 17.5 kelvin above the 5 °C middle of a 2–8 °C refrigerator. The ten-degree rule of thumb — degradation rate roughly doubling per 10 K — puts that at about 3.4 times the refrigerated rate. It is an order-of-magnitude statement about a rate, not a shelf life, and the top of the 20–25 °C band runs about 1.4 times faster than the bottom of it. Whatever you find, check what was measured before you use it: a paper reporting purity at room temperature has not measured content, and the two fail at different rates for different reasons.

The short version: water enables most of it, oxygen enables oxidation, surfaces enable adsorption, and agitation enables aggregation.

Oxidation targets methionine, cysteine and tryptophan, adding sixteen daltons per oxygen. It is catalysed by trace metals and promoted by dissolved oxygen and by light.

Reported and extrapolated stability by condition

Windows for the solid state are chemical; windows for solution are microbiological and usually shorter than the chemical limit.

It helps to be literal here: deamidation converts asparagine or glutamine to the corresponding acid via a succinimide intermediate, adding one dalton. It is base-catalysed, accelerates above neutral pH and is the dominant aqueous pathway for many peptides.

Metal-catalysed oxidation of methionine is documented across peptide and protein formulations and is why chelators appear in some formulations.

Sequence decides which pathways are even available. Check the residues.

Answering this needs the physical state, since a dry powder is protected from most of these and a solution is protected from none.

Freeze-thaw cycling drives aggregation through concentration at the ice interface and pH shifts as buffer components crystallise out at different rates. Each cycle costs something.

A mass spectrum resolves most of this: minus eighteen is dehydration or succinimide, plus one is deamidation, plus sixteen is oxidation, and an unchanged mass with a shifted retention time is an isomer.

Adsorption losses at low concentrations are quantified in formulation studies and are the reason carrier proteins are used in dilute preparations.

At dilute concentrations, suspect adsorption before you suspect chemistry.

edited 2 Apr 2025 by Dr_Rosalind_Achebe — removed a claim I could not source

This is answerable from the chemistry rather than from anecdote, which is unusual and welcome.

Aggregation is physical: peptides unfold at air-liquid interfaces and associate. Shaking maximises that interface, which is why swirling and shaking produce visibly different outcomes on the same vial.

Concretely, adsorption onto glass and plastic is significant at low concentrations — micrograms per millilitre — and negligible at milligrams per millilitre. It is the usual explanation for an apparent loss in a dilute preparation.

Apparent loss in a dilute preparation is usually adsorption rather than degradation and is worth ruling out first.

A mass spectrum names the pathway. Plus one, plus sixteen, minus eighteen.

The honest answer is that most reported "degradation" is adsorption and dilution error rather than chemistry.

Light exposure matters for tryptophan-containing sequences and for anything with a chromophore. Amber vials and a closed box are free mitigations.

Aggregation at air-liquid interfaces is established from surface-tension and particle-count studies and is the basis for anti-agitation handling guidance.

Cold, dry, dark, still. Those four words cover most of the mitigation.

edited 2 Feb 2025 by kwn_analytical — updated for the 2026 guidance change

To be exact about it, asparagine and glutamine are the deamidation risk, and methionine is the oxidation risk.

Hydrolysis cleaves the backbone, most readily at aspartate-proline and aspartate-glycine sequences, and is acid-catalysed. In a dry solid it barely proceeds at all.

Deamidation via the succinimide intermediate is well characterised, with sequence-dependent rates highest for asparagine-glycine motifs.

Swirl, never shake. Aggregation is a handling problem more than a time problem.