The half-life question, answered properly
What the pharmacokinetic data supports about dose timing, missed doses and interruption.
Semaglutide
Page 15 of 18 of this archive, newest first.
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.
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.
Why "muscle-sparing" is a marketing term and not a measurement
The gap between a defensible recommendation and a confident one is where most of the harm in this subject lives.
What the protein literature actually shows, and in whom it was shown
Where the familiar figures come from, what populations they were measured in, and how far the extrapolation reaches.
One receptor, several signals: the case for reading retatrutide as a biased agonist
What the in-vitro data supports, what it does not, and where the extrapolation to a person begins.
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.
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.
Escalating past the approved maximum, examined honestly
Where the curve flattens, what flattens with it, and what does not.
Maximum tolerated is not maximum approved
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
What the cagrilintide schedule assumes about a person it has never met
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
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.
Why people actually stop, in the order they actually stop
A supply interruption is a discontinuation with no notice, no taper and no plan. That is a distinct clinical situation.
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 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.
Target dose, effective dose, and the distance between them
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.
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.
Bone density during rapid weight loss: what is known, which is less than you would hope
Weight loss reduces bone mineral density at load-bearing sites. Whether that translates into fractures in this population is unmeasured.
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.
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.