Where the receptor is: a tissue-by-tissue account of tirzepatide’s reach
The same receptor population that produces the therapeutic effect produces the commonest adverse one.
Explainers
Page 9 of 12 of this archive, newest first.
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From cell to clinic: where the extrapolation stops being safe
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
Twelve minutes or forty: what gradient slope buys
A shallow gradient resolves impurities that a steep one runs into the parent peak. Both methods are legitimate; only one of them can see the small stuff.
Longer is not safer
The insulin injection-technique literature is large, well conducted and directly transferable on questions of depth and tissue. We say where it stops transferring.
Gallstones during rapid weight loss: drug, or weight loss?
Pancreatitis is rare, was adjudicated in the outcome programmes, and did not show the imbalance early case reports suggested.
Errors ranked by how much dose they move
The most dangerous errors are the ones that leave no trace: nothing looks wrong, the mark is in the same place, and the dose is wrong by an order of magnitude.
What orthogonal actually means, and what it does not
An orthogonal method separates on a different physical principle, so that species co-eluting in the first are likely to resolve in the second. Two runs of the same method at…
The incretin receptors, ranked by how much we actually know about them
The class is described as though every molecule in it did the same thing. At the receptor, they demonstrably do not.
Six tells, in order of how quickly they can be checked
A blank certificate with the numbers left editable is an ordinary internal document. Its circulation as a finished record is the problem.
A schedule that bends does not break
Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.
A peak with no chromophore is a peak with no peak
Non-chromophoric components — counter-ions, salts, some excipients — contribute mass to the vial and nothing at all to the chromatogram.
Residual stomach content on endoscopy: the studies
This is the single interaction with ordinary medical care that patients most need to disclose, and it is the one most often not asked about.
Two decimal places on a single injection is a rhetorical choice
The arithmetic of significant figures, applied to a document that routinely reports four of them.
Lipohypertrophy, and the absorption it ruins
A rotation scheme that is too complicated will not be followed. We describe the simple ones that are.
The incretin receptors, ranked by how much we actually know about them
The receptor is expressed in more tissues than the popular account allows, and that is the whole story.
The arithmetic behind every identity confirmation, worked in full
A peptide has a monoisotopic mass and an average mass, they differ by several daltons at this molecular size, and a certificate that does not say which it quotes cannot be…
Twelve minutes or forty: what gradient slope buys
We set out the parameters a method disclosure would contain, all of which are known to whoever ran the sample and none of which is commercially sensitive.
What competing on one number does to a market
A market that competes on one measurement will optimise that measurement. There are legitimate ways to raise a purity figure that involve no change to the product at all.
The limits of mechanism: why receptor data will not tell you who responds
A catalogue of open questions, with an assessment of how likely each is to be resolved.
Pass, conform, comply: three words for three different claims
Statements of conformity are supposed to rest on a stated decision rule. Almost nothing in this trade states one.