Load, not cardio: the distinction the general advice keeps losing
The older-adult diet-and-exercise trials are the closest analogue to rapid pharmacological weight loss, and they are twenty years old.
Semaglutide
Page 3 of 18 of this archive, newest first.
What the trials monitored, and what that implies about routine practice
What the pivotal programmes measured and how often, which is a more defensible template than most published monitoring schedules.
One receptor, several signals: the case for reading semaglutide as a biased agonist
A tour of what happens in the thirty seconds after binding, and why it matters at week thirty.
How a peptide that lasts seven days binds a receptor that recycles in minutes
What the in-vitro data supports, what it does not, and where the extrapolation to a person begins.
Reading the mazdutide titration schedule as a regulatory artefact
What the regulatory dossiers actually contain on dose selection is remarkably thin, and worth knowing before treating the ladder as settled science.
Bone density during rapid weight loss: what is known, which is less than you would hope
The evidence base is one secondary analysis, several small studies and a large amount of extrapolation from bariatric surgery.
The half-life question, answered properly
Half-life, accumulation ratio and time to steady state are three separate quantities, and confusing them produces most of the bad advice in circulation.
Why "muscle-sparing" is a marketing term and not a measurement
Almost every practical recommendation in circulation was established in a population that does not resemble the people now following it.
What STEP 4 and SURMOUNT-4 actually established
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
The limits of mechanism: why receptor data will not tell you who responds
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
What the trial protocols permitted, and what the labels omitted
Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.
Sarcopenia is a diagnosis, not a synonym for losing lean mass
The rule that a quarter of weight lost is lean tissue has been in textbooks for decades and does not survive close reading.
Target dose, effective dose, and the distance between them
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
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.
Coming off: what the pharmacology permits
What a slow reduction could plausibly buy, and what it certainly cannot prevent.
The brainstem does most of the work
A tour of the tissues where the receptor is expressed, and what happens in each.
Reading the survodutide titration schedule as a regulatory artefact
What the regulatory dossiers actually contain on dose selection is remarkably thin, and worth knowing before treating the ladder as settled science.
Why people actually stop, in the order they actually stop
The trials studied planned withdrawal. Almost nobody stops that way.
What the older diet-and-exercise trials found in the hip
The evidence base is one secondary analysis, several small studies and a large amount of extrapolation from bariatric surgery.
Why your laboratory interval differs from the one in the textbook
Two sources of noise sit under every number: how reproducible the assay is, and how much the analyte varies within the same person on the same day.