Which results should be repeated before they are investigated
What the pivotal programmes measured and how often, which is a more defensible template than most published monitoring schedules.
Tirzepatide
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A reference interval is not a target, and a result outside one is not a diagnosis
Almost every misreading of a laboratory panel is a misunderstanding of what a reference interval is and how much a result has to move before the movement means anything.
Gastric emptying is a mechanism, not a side effect
The central effects are not a bonus. On the current evidence they are the principal mechanism of weight loss.
The eighteenth month, and the conversation that should have happened in the third
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
What the older diet-and-exercise trials found in the hip
A plausible mechanism, a measurable change, and no outcome data. This is what an open question looks like.
The dose that got you here and the dose that keeps you here
Every withdrawal trial compared full dose against nothing. The clinically interesting comparison — full dose against a reduced one — has not been randomised.
The three-times-upper-limit convention, and where it came from
What the renal and hepatic outcome programmes actually measured, and over what duration.
The restart nobody plans for
We work through the residual-exposure table so the decision can be made from numbers rather than from feel.
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.
Coming off: what the pharmacology permits
What a slow reduction could plausibly buy, and what it certainly cannot prevent.
The eighteenth month, and the conversation that should have happened in the third
What the trials measured was continuation against withdrawal. What patients want to know is continuation at a lower dose, and that study has largely not been done.
Holding a dose is a decision, not a failure
Every major phase 3 protocol in this class allowed escalation to be delayed for tolerability. Almost no product label explains the mechanics of doing so.
What the upper limit of normal for ALT should be, and why it is not
The reference interval for alanine aminotransferase in most laboratories is derived from a population that included people with undiagnosed fatty liver.
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.
Diminishing returns, quantified
Where the curve flattens, what flattens with it, and what does not.
Load, not cardio: the distinction the general advice keeps losing
What was supervised, at what frequency, at what intensity, and for how long.
The dose that got you here and the dose that keeps you here
Dose reduction is not withdrawal, and the trials that tested withdrawal cannot be read as testing it.
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.
Do you need the top of the ladder?
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
What the trial protocols permitted, and what the labels omitted
The practice is near-universal, clinically sensible, and supported by observational data rather than randomised comparison. We say which is which.