Seasonal use, holiday use, and the honest state of the evidence
The vocabulary is borrowed, the rationale is usually mechanistic, and the outcome data does not exist.
Tirzepatide
Page 15 of 18 of this archive, newest first.
Why people actually stop, in the order they actually stop
The trials studied planned withdrawal. Almost nobody stops that way.
Bone density during rapid weight loss: what is known, which is less than you would hope
Density is a proxy for strength and an imperfect one, particularly when soft-tissue thickness over the measurement site is changing.
What a low result means when intake has halved
What the trials measured, which in the case of micronutrients is very little.
A missed dose, modelled: what happens to liraglutide concentrations over the following fortnight
Half-life, accumulation ratio and time to steady state are three separate quantities, and confusing them produces most of the bad advice in circulation.
The half-life question, answered properly
What the pharmacokinetic data supports about dose timing, missed doses and interruption.
A schedule that bends does not break
Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.
What STEP 3 tells us about maintenance, and what it does not
Every withdrawal trial compared full dose against nothing. The clinically interesting comparison — full dose against a reduced one — has not been randomised.
Grams per kilogram of what? The denominator problem in protein guidance
Where the familiar figures come from, what populations they were measured in, and how far the extrapolation reaches.
Three weeks off is a fresh start, whether or not you want one
Supply interruption is the commonest cause of unplanned re-titration in this market, and it is almost never framed that way.
Micronutrient monitoring: which panel, how often, and on whose evidence
What the trials measured, which in the case of micronutrients is very little.
Which results are findings and which are consequences of the weight loss
Three different explanations for the same abnormal number, and how to tell them apart.
A schedule that bends does not break
Reducing a dose is not going backwards. In a tolerability-limited class it is the mechanism by which the ceiling is found.
Escalating past the approved maximum, examined honestly
Where the curve flattens, what flattens with it, and what does not.
Why "muscle-sparing" is a marketing term and not a measurement
The rule that a quarter of weight lost is lean tissue has been in textbooks for decades and does not survive close reading.
What we would need to randomise to answer this properly
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.
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
Weight reduction in the long programmes flattens at roughly sixty to seventy-two weeks. The timing is consistent, predictable and almost never mentioned in advance.
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.
Tapering: a word borrowed from drugs with withdrawal syndromes
These agents produce no dependence and no withdrawal syndrome. What a taper would be for is therefore a real question rather than an obvious one.