The dose you were told to reach and the dose you will actually stay on
The published ladder exists because a protocol needed a single number. Practice has never followed it exactly, and the regulatory file never assumed it would.
Tirzepatide
Page 11 of 18 of this archive, newest first.
The glucagon receptor arm, and why it is the hardest to reason about
What adding GIP activity does, on the current evidence, and what remains unresolved.
How a peptide that lasts seven days binds a receptor that recycles in minutes
A tour of what happens in the thirty seconds after binding, and why it matters at week thirty.
What STEP 5 tells us about maintenance, and what it does not
The commonest real-world strategy in this drug class is the least studied one.
Holding a dose is a decision, not a failure
Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.
Why the bone question is harder than the muscle question
A plausible mechanism, a measurable change, and no outcome data. This is what an open question looks like.
The arithmetic of a step: what doubling a dose actually asks of you
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
HbA1c and its lag: what a result three months old is telling you
A robust, cheap, standardised assay with a specific and well-catalogued set of failure modes, several of which are common in this population.
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 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 of evidence in this area.
Non-responders, and the honest state of the evidence about them
The mechanism is well described. The variance is not.
What we would need to measure to explain the response distribution
The mechanism is well described. The variance is not.
Three weeks off is a fresh start, whether or not you want one
Concentrations fall by half a week, so a month away leaves a small fraction of steady state. Resuming at the previous dose presents the receptor with a step it has not seen…
Least significant change: the number your body-composition printout omits
The compartment called lean mass contains water, glycogen, viscera and skin. Only some of it is the tissue anybody is worried about.
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.
The visceral fat result nobody quotes, from the substudy everybody cites
The trials measured mass. Nobody measured whether the participants got weaker.
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.
Why a drug that acts on the pancreas changes what food tastes like
A tour of the tissues where the receptor is expressed, and what happens in each.
The kidney, the heart and the receptor nobody was looking for
The same receptor population that produces the therapeutic effect produces the commonest adverse one.
The lead-in, the randomisation, and the year that followed
A withdrawal trial answers a narrower question than it appears to. This piece states which question.