Gallstones during rapid weight loss: drug, or weight loss?
We give background rates alongside trial rates, because an event occurring during treatment is not thereby caused by it.
Volume I
Every issue published in 2024 — 12 numbers, 2,040 pieces.
Features in Volume 1
Why a dead-clean sterile filter can pass pyrogen straight through
The limit for a parenteral product is calculable from the dose and the body weight in two lines. Almost nobody in this trade performs the calculation.
Why people actually stop, in the order they actually stop
Real-world persistence figures, with their definitions stated, because the definitions are doing most of the work.
Oxidation, and the peroxide that came in with the surfactant
An isoaspartate rearrangement changes the molecule and not the mass. A method that confirms identity by molecular weight alone will report it as the parent compound.
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.
What changing your injection day does to tirzepatide exposure, and what it does not
What the pharmacokinetic data supports about dose timing, missed doses and interruption.
A reference interval is not a target, and a result outside one is not a diagnosis
The arithmetic of the reference change value, worked for the analytes that matter here.
We split six vials four ways and posted them
The Journal submitted split samples from single lots to three assay services, under names unconnected to this publication, and published each method alongside each result.
The supply gap as a clinical event
The trials studied planned withdrawal. Almost nobody stops that way.
One vial, four weeks, and the data that does not exist
Every degradation pathway accelerates by orders of magnitude on reconstitution, because the solvent that lyophilisation removed is the reagent most of them need.
Maintenance dosing: what is licensed, what is practised, and what is evidenced
Dose reduction is not withdrawal, and the trials that tested withdrawal cannot be read as testing it.
Benzyl alcohol is a preservative, not a sterilising agent
At low concentrations a measurable fraction of peptide can adsorb to glass and plastic surfaces, and the loss is largest exactly where it is least expected.
Check the vial, not the box
A document is only as good as the chain that connects it to the material, and most chains here are two or three links longer than the paperwork admits.
Non-responders, and the honest state of the evidence about them
The mechanism is well described. The variance is not.
Disregard limits: what a regulated laboratory does with a tiny peak
Chromatographic software does not integrate every fluctuation in the baseline. It applies a threshold, and the threshold changes the reported purity by amounts that matter…
What the older diet-and-exercise trials found in the hip
Weight loss reduces bone mineral density at load-bearing sites. Whether that translates into fractures in this population is unmeasured.
Why a result on one vial says less than the trade needs it to
A result on one vial generalises to a batch only if the vial was drawn in a way that makes it representative — and nobody records how it was drawn.
What the placebo arms of the withdrawal trials actually tell us
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
Twenty-eight days is a number from somebody else’s product
Bacteriostatic water contains benzyl alcohol at 0.9 per cent, which inhibits microbial growth in a preserved multiple-dose presentation. It does not sterilise a contaminated…
Vitamin D, adiposity, and a volume-of-distribution problem
A monitoring schedule requires evidence about incidence. For this population, that evidence does not exist.
Deamidation is the commonest degradation route and the hardest to see
We describe each pathway in enough chemical detail to explain why it is invisible to the method the trade uses, because that is the part which has practical consequences.
The kidney, the heart and the receptor nobody was looking for
The central effects are not a bonus. On the current evidence they are the principal mechanism of weight loss.
What STEP 4 and SURMOUNT-4 actually established
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
The supplement trade found this drug class quickly, and the citations did not improve
A survey of what the meta-analyses support, with the populations named.