Reading HbA1c in the presence of anaemia
A robust, cheap, standardised assay with a specific and well-catalogued set of failure modes, several of which are common in this population.
Tirzepatide
Page 16 of 18 of this archive, newest first.
What STEP 4 tells us about maintenance, and what it does not
The commonest real-world strategy in this drug class is the least studied one.
The shortage years, and what they taught about interruption
Real-world persistence figures, with their definitions stated, because the definitions are doing most of the work.
What the placebo arms of the withdrawal trials actually tell us
The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately randomised it.
Non-responders, and the honest state of the evidence about them
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
A missed dose, modelled: what happens to retatrutide concentrations over the following fortnight
An accumulation model, drawn from published parameters, with its assumptions stated.
Vitamin D, adiposity, and a volume-of-distribution problem
Micronutrient guidance for this drug class is borrowed almost entirely from post-bariatric surveillance, where the anatomy is different and the deficiency mechanisms are not…
What happens when the drug is taken away: three randomised answers
The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately randomised it.
Dual, triple, co-formulated: a taxonomy the coverage keeps collapsing
Head-to-head data exists for some of these comparisons and not for others. This piece says which.
Why the bone question is harder than the muscle question
What the Journal would want measured before treating this as settled in either direction.
What STEP 3 measured, and what it was never powered to detect
What was pre-specified, what was exploratory, and what was calculated afterwards by people who did not run the trial.
Thiamine and the vomiting patient
Which markers are informative, which are confounded, and which move for reasons unrelated to nutrition.
Grams per kilogram of what? The denominator problem in protein guidance
The practical difficulty is not knowing the target. It is meeting it on an appetite that has been pharmacologically reduced by half.
Vitamin D, adiposity, and a volume-of-distribution problem
Reduced intake is a plausible mechanism for deficiency. Reduced absorption is not, and the two are conflated in most of the advice.
What a month without the drug does to tolerability
The convention — resume lower, re-escalate — is not caution. It follows directly from the elimination half-life.
What SURMOUNT-1 tells us about maintenance, and what it does not
A survey of the maintenance evidence, which is shorter than the survey of the withdrawal evidence.
Diminishing returns, quantified
The ceiling in this class is anatomical: the same receptor populations that suppress appetite provoke nausea, and they saturate together.
The dose that got you here and the dose that keeps you here
What the labels permit, what clinicians do, and the size of the gap between them.
What the GLP-1 receptor actually does when mazdutide binds it
Selectivity, potency and efficacy are three different measurements. The trade routinely reports none of them.
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.