March 2026

Antiemetics, laxatives and the thin literature underneath them

Dietary measures are widely recommended, plausible on mechanism, and supported mainly by observational data and clinical…

What we would need to measure to explain the response distribution

The mechanism is well described. The variance is not.

Pancreatitis, obstruction, gallbladder: three things nausea can be

Rapid weight loss by any means raises gallstone risk. Separating that from a direct drug effect requires a comparator, and the…

What actually helps, ranked by evidence

Dietary measures are widely recommended, plausible on mechanism, and supported mainly by observational data and clinical…

GIP was a failed target for thirty years. Then it was not.

A dual agonist is one molecule with two receptor activities. A co-formulation is two molecules in one pen. The coverage treats…

One receptor, several signals: the case for reading semaglutide as a biased agonist

A tour of what happens in the thirty seconds after binding, and why it matters at week thirty.

How a peptide that lasts seven days binds a receptor that recycles in minutes

What the in-vitro data supports, what it does not, and where the extrapolation to a person begins.

Holidays, surgery, sickness: interruption in practice

Supply interruption is the commonest cause of unplanned re-titration in this market, and it is almost never framed that way.

Oxidation, and the peroxide that came in with the surfactant

We describe each pathway in enough chemical detail to explain why it is invisible to the method the trade uses, because that is…

Twenty-eight days is a number from somebody else’s product

We set out what is known, what is inferred and what is simply assumed about the fortnight after a vial is opened.

Low endotoxin recovery: the interference nobody looks for

The limit for a parenteral product is calculable from the dose and the body weight in two lines. Almost nobody in this trade…

An interlaboratory comparison nobody had run

Duplicate submissions under different names test within-laboratory repeatability, which is a different quantity from…

Accreditation, scope, and the question nobody asks Medutest

What the Journal asks when a document arrives unsigned, and what the answers have been.

Endotoxin is not a microorganism, and killing the bacteria does not remove it

Three compendial method families are in routine use and a fourth, based on a recombinant enzyme rather than crab lysate, is now…

Accreditation, scope, and the question nobody asks PeptideMeter

A manufacturer’s certificate is a self-declaration. An accredited laboratory’s report is a third-party measurement. The trade…

The degradation product that elutes underneath the parent peak

The sequence predicts the failure mode. A methionine predicts oxidation; an asparagine followed by a glycine predicts…

The supplement trade found this drug class quickly, and the citations did not improve

The resistance-training and energy-deficit literature supports a higher protein intake. None of it was conducted in people…

The advice is mostly reasonable. The certainty is not earned.

The gap between a defensible recommendation and a confident one is where most of the harm in this subject lives.

Which results are findings and which are consequences of the weight loss

A substantial proportion of the abnormal results generated during rapid weight loss are consequences of the weight loss rather…

Lean mass is a compartment, not a tissue

The instrument determines the answer more than the drug does, and the trade quotes the answer without naming the instrument.

The one randomised trial that combined an incretin with supervised exercise

One randomised trial has combined a GLP-1 receptor agonist with supervised exercise. Its result is the single most useful piece…

What the trials monitored, and what that implies about routine practice

What the pivotal programmes measured and how often, which is a more defensible template than most published monitoring schedules.

The skeleton responds to load, and load is falling

What the Journal would want measured before treating this as settled in either direction.

The retest date and the expiry date are not the same document

A retest date says that material should be re-examined before use. An expiry date says it should not be used. The trade uses the…

Nought point nine eight of a dalton: the modification that hides in plain sight

What would be needed to catch each of these, and what it would cost.

The degradation product that elutes underneath the parent peak

Deamidation, oxidation, aggregation and hydrolysis account for nearly all of what happens to a peptide over time. Each has a…

The generic peptide method, and what it was designed for

A shallow gradient resolves impurities that a steep one runs into the parent peak. Both methods are legitimate; only one of them…

The header, the table and the signature block

The header identifies the batch, the table records the tests, and the footer says who is answerable. Two of the three are…

What the four services actually offer, test by test

We asked all four services what they can determine, on what timescale, at what price, and under what accreditation. The answers…

Same material, different gradients, different answers

Two years ago we ran an anonymised version of this comparison and promised a named one. This is it, with every method printed in…

Continued treatment against continued placebo: the comparison that settled it

The regain trajectories, arm by arm, with the estimands named.

The upper rungs, ranked by evidence

Where the curve flattens, what flattens with it, and what does not.

Target dose, effective dose, and the distance between them

A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.

The imaging substudy is an afterthought in the protocol and the centrepiece of the debate

The composition data comes from imaging substudies enrolling a few score participants at selected sites. It is the best evidence…

Storage after reconstitution, and the evidence behind the numbers

Sharps disposal is a legal obligation in most jurisdictions and a safety obligation everywhere. Household waste is not a route.

Load, not cardio: the distinction the general advice keeps losing

The older-adult diet-and-exercise trials are the closest analogue to rapid pharmacological weight loss, and they are twenty…

A unit is not a dose, and it never was

Insulin syringes are graduated in units on a convention that fixes 100 units to one millilitre. That convention says nothing…

Custody, condition and the temperature nobody logged

The condition on arrival is recorded by some services and not others, and it is one of the more informative lines in a report.

The dose that got you here and the dose that keeps you here

A survey of the maintenance evidence, which is shorter than the survey of the withdrawal evidence.

A design note on withdrawal trials, and why the run-in matters

The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately…

REWIND was built to answer the stopping question, and it did

Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are…

An interlaboratory comparison nobody had run

Two years ago we ran an anonymised version of this comparison and promised a named one. This is it, with every method printed in…

Randomised withdrawal is the cleanest design in this field and the least discussed

Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are…

The submitted sample: the weakest link in the whole system

What a laboratory can and cannot know about the provenance, storage history and representativeness of what lands on its bench.

The skeleton responds to load, and load is falling

Weight loss reduces bone mineral density at load-bearing sites. Whether that translates into fractures in this population is…

What happens to a stopper after the fourth needle

Particulate matter is the oldest quality attribute in injectable manufacture and the one a private buyer is best placed to…

Lipohypertrophy, and the absorption it ruins

Repeated injection into the same small area produces lipohypertrophy — thickened, rubbery subcutaneous tissue with blunted and…

Aseptic technique for people who were never taught it

For licensed products the in-use period is established by stability data. For a peptide reconstituted at home there is no such…

Measuring more frequently generates more flags and not more information

The argument for a baseline panel is that it makes every subsequent result interpretable. The argument against frequent…

What a reference standard is, and what an in-house standard is not

Matching a retention time against a standard is evidence of consistency, not proof of identity. Two different species can elute…

What orthogonal actually means, and what it does not

The most useful single addition to any purity determination is a second separation under a different pH or on a different…

Nine parcels, nine loggers, and one uncomfortable set of traces

The compendial definitions of cold, controlled cold and controlled room temperature permit specified excursions, and knowing the…

The mechanism behind the mechanism

Delayed gastric emptying is a mechanism that becomes an adverse effect above a threshold. It is not a complication in the…

What a month without the drug does to tolerability

Concentrations fall by half a week, so a month away leaves a small fraction of steady state. Resuming at the previous dose…

The interventions with trial support, and the much longer list without

Almost nothing in the standard management repertoire has been tested in a randomised trial in this specific population. We say…

One receptor, several signals: the case for reading liraglutide as a biased agonist

Receptor pharmacology explains more of the clinical picture than the dose does — and almost none of it appears in the material…

A named analyst is the cheapest quality signal in this trade

Somebody has to be answerable for a release document. On most certificates in this market, nobody is named at all.

The same signature, the same peak, three different batches

A blank certificate with the numbers left editable is an ordinary internal document. Its circulation as a finished record is the…

Reading the mazdutide titration schedule as a regulatory artefact

What the regulatory dossiers actually contain on dose selection is remarkably thin, and worth knowing before treating the ladder…

The chromatogram that appears on four documents

A PDF carries metadata about the software that produced it, and that metadata is frequently more informative than the content.