Stated plainly: orforglipron · 20 mg/mL · sixteen weeks.
This is asserted often enough that I assumed it was established, and then I went looking for the source.
I have searched the primary literature and found one paper that is adjacent but not on point.
Can anyone point me at a primary source, or confirm that there is not one?
sixteen weeks is 112 days and, on a weekly schedule, 16 stopper punctures out of one vial at 20 mg/mL. Set the chemical question aside for a moment, because the puncture count is the one with a convention attached: 112 days is 4 times the twenty-eight days conventionally allowed for a preserved multi-dose preparation once it has been entered. Chemically, 20 mg/mL is high enough that adsorption to the glass is a rounding error and low enough that it is not protecting you from anything. What 16 withdrawals do add is 16 opportunities to introduce air, 16 coring events on the same stopper, and a headspace that grows with every draw — none of which show up on a certificate and all of which are avoided by splitting into aliquots at reconstitution.
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.
| State | Condition | Usable window | Basis |
|---|---|---|---|
| Lyophilised solid | −20 °C, sealed, dry | 24–36 months | Supplier guidance |
| Lyophilised solid | 2–8 °C, sealed | 12–24 months | Supplier guidance |
| Lyophilised solid | 25 °C, sealed | 4–8 weeks | Extrapolated (Arrhenius) |
| Lyophilised solid | 40 °C, sealed | 1–2 weeks | Extrapolated |
| Solution, preserved | 2–8 °C | 28 days | USP microbiological convention |
| Solution, preserved | 25 °C | 3–7 days | Extrapolated |
| Solution, unpreserved | 2–8 °C | 24 hours | USP microbiological convention |
Windows for the solid state are chemical; windows for solution are microbiological and usually shorter than the chemical limit.
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.
Metal-catalysed oxidation of methionine is documented across peptide and protein formulations and is why chelators appear in some formulations.
Nothing here is medical advice, and research-use compounds are not approved for human use.
Swirl, never shake. Aggregation is a handling problem more than a time problem.
Analytical standards and reagents with traceable certificates. Every quantitative result you read inherits the accuracy of the standard behind it.
Shop standardsThe honest answer is that most reported "degradation" is adsorption and dilution error rather than chemistry.
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.
The relevant detail is that 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.
At dilute concentrations, suspect adsorption before you suspect chemistry.
edited 23 Jul 2026 by claudia_ferrante — updated for the 2026 guidance change
Start with the sequence, because which pathways are available depends on which residues are present.
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.
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.
Adsorption losses at low concentrations are quantified in formulation studies and are the reason carrier proteins are used in dilute preparations.
A mass spectrum names the pathway. Plus one, plus sixteen, minus eighteen.
Answer first: the degradation pathways worth knowing are hydrolysis, deamidation, oxidation, aggregation and adsorption, and each has a different trigger and a different mitigation.
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.
Cold, dry, dark, still. Those four words cover most of the mitigation.
Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.