The trade has decided the ceiling is arbitrary. The trials disagree.
The ceiling in this class is anatomical: the same receptor populations that suppress appetite provoke nausea, and they saturate together.
Semaglutide
Page 17 of 18 of this archive, newest first.
The ceiling is a tolerability finding, not an efficacy one
Where the curve flattens, what flattens with it, and what does not.
The shortage years, and what they taught about interruption
A supply interruption is a discontinuation with no notice, no taper and no plan. That is a distinct clinical situation.
What the outcome trials measured in the kidney
Asymptomatic pancreatic enzyme elevation is common on treatment and is not pancreatitis. The distinction is clinical, not biochemical.
Which results should be repeated before they are investigated
What the pivotal programmes measured and how often, which is a more defensible template than most published monitoring schedules.
Why the bone question is harder than the muscle question
What the Journal would want measured before treating this as settled in either direction.
Seasonal use, holiday use, and the honest state of the evidence
What the exposure arithmetic says about a fortnightly schedule, and where the arithmetic stops being informative.
The one-quarter rule, and the paper that took it apart
The gap between a defensible recommendation and a confident one is where most of the harm in this subject lives.
Escalating past the approved maximum, examined honestly
Where the curve flattens, what flattens with it, and what does not.
Side effects, cost, supply, target: four reasons with four trajectories
Real-world persistence figures, with their definitions stated, because the definitions are doing most of the work.
What SURPASS-3 tells us about maintenance, and what it does not
What the labels permit, what clinicians do, and the size of the gap between them.
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.
The escalation table is the thinnest page in the label
The published ladder exists because a protocol needed a single number. Practice has never followed it exactly, and the regulatory file never assumed it would.
A guide to the results that will resolve themselves
Three different explanations for the same abnormal number, and how to tell them apart.
Why the bone question is harder than the muscle question
Weight loss reduces bone mineral density at load-bearing sites. Whether that translates into fractures in this population is unmeasured.
Why receptor selectivity is the least discussed number in incretin pharmacology
Selectivity, potency and efficacy are three different measurements. The trade routinely reports none of them.
Why people actually stop, in the order they actually stop
Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.
Albumin, fatty-acid chains, and the engineering that made a weekly incretin possible
The molecular engineering that turned a peptide with a two-minute half-life into a once-weekly drug.
What has to change before a change has happened
A flag is a probability statement about a population. It is not a statement about the person holding the printout.
Stepping down is part of titration
The practice is near-universal, clinically sensible, and supported by observational data rather than randomised comparison. We say which is which.