A schedule that bends does not break
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.
Semaglutide
Page 16 of 18 of this archive, newest first.
What STEP 3 measured, and what it was never powered to detect
What was pre-specified, what was exploratory, and what was calculated afterwards by people who did not run the trial.
GIP was a failed target for thirty years. Then it was not.
A dual agonist is one molecule with two receptor activities. A co-formulation is two molecules in one pen. The coverage treats them as synonyms.
GIP was a failed target for thirty years. Then it was not.
What adding GIP activity does, on the current evidence, and what remains unresolved.
Sarcopenia is a diagnosis, not a synonym for losing lean mass
The gap between a defensible recommendation and a confident one is where most of the harm in this subject lives.
The supply gap as a clinical event
Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.
The three-times-upper-limit convention, and where it came from
Asymptomatic pancreatic enzyme elevation is common on treatment and is not pancreatitis. The distinction is clinical, not biochemical.
The advice is mostly reasonable. The certainty is not earned.
Grading six widely repeated claims against the studies actually behind them.
What the upper limit of normal for ALT should be, and why it is not
Estimated glomerular filtration rate is a calculation with muscle mass in the denominator of its assumptions. In this population that matters.
Holidays, surgery, sickness: interruption in practice
The convention — resume lower, re-escalate — is not caution. It follows directly from the elimination half-life.
What SURMOUNT-1 tells us about maintenance, and what it does not
A survey of the maintenance evidence, which is shorter than the survey of the withdrawal evidence.
The three-times-upper-limit convention, and where it came from
Asymptomatic pancreatic enzyme elevation is common on treatment and is not pancreatitis. The distinction is clinical, not biochemical.
HbA1c and its lag: what a result three months old is telling you
HbA1c integrates roughly three months of glycaemia with the most recent weeks weighted most heavily. Almost every misreading of it is a misreading of that weighting.
What STEP 4 and SURMOUNT-4 actually established
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
What the GLP-1 receptor actually does when mazdutide binds it
Selectivity, potency and efficacy are three different measurements. The trade routinely reports none of them.
Thiamine and the vomiting patient
What the trials measured, which in the case of micronutrients is very little.
SURPASS-3 was built to answer the stopping question, and it did
What was withdrawn, from whom, after how long, and what was measured afterwards.
From 0.25 to 2.4: reading a ladder as a series of ratios
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
The supply gap as a clinical event
Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.
Escalating past the approved maximum, examined honestly
The ceiling in this class is anatomical: the same receptor populations that suppress appetite provoke nausea, and they saturate together.