When a symptom is information and when it is noise
The practice is near-universal, clinically sensible, and supported by observational data rather than randomised comparison. We say which is which.
Tirzepatide
Page 10 of 18 of this archive, newest first.
Why the bone question is harder than the muscle question
Density is a proxy for strength and an imperfect one, particularly when soft-tissue thickness over the measurement site is changing.
Six things incretin pharmacology cannot currently predict
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
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.
A few hundred participants carry the whole body-composition argument
What was pre-specified, what was exploratory, and what was calculated afterwards by people who did not run the trial.
Micronutrient monitoring: which panel, how often, and on whose evidence
A monitoring schedule requires evidence about incidence. For this population, that evidence does not exist.
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.
Which results are findings and which are consequences of the weight loss
The estimated glomerular filtration rate is calculated from creatinine, creatinine comes from muscle, and muscle mass is falling. The arithmetic is unforgiving.
The restart nobody plans for
We work through the residual-exposure table so the decision can be made from numbers rather than from feel.
Sarcopenia is a diagnosis, not a synonym for losing lean mass
Almost every practical recommendation in circulation was established in a population that does not resemble the people now following it.
The shortage years, and what they taught about interruption
The trials studied planned withdrawal. Almost nobody stops that way.
Stepping down is part of titration
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.
A year after stopping: what the trials found at the far end
Fat mass, lean mass, and the composition of regained weight — the thinnest literature in this piece.
The trade has decided the ceiling is arbitrary. The trials disagree.
Higher doses of these molecules have been studied. In general they produced modest additional efficacy and disproportionate additional symptom burden, which is why the…
What the GLP-1 receptor actually does when tirzepatide binds it
The class is described as though every molecule in it did the same thing. At the receptor, they demonstrably do not.
Side effects, cost, supply, target: four reasons with four trajectories
Why the reason for stopping changes what happens afterwards.
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.
Amylin is not an incretin, and cagrilintide is not a GLP-1 agonist
The glucagon arm raises energy expenditure and also raises hepatic glucose output. Balancing those is the whole engineering problem.
What a month without the drug does to tolerability
The convention — resume lower, re-escalate — is not caution. It follows directly from the elimination half-life.
The steps get smaller as the ladder gets higher, and that is deliberate
What the published pharmacokinetics permit, what the labels state, and where the two diverge.