Diminishing returns, quantified
The ceiling in this class is anatomical: the same receptor populations that suppress appetite provoke nausea, and they saturate together.
Tirzepatide
Page 4 of 18 of this archive, newest first.
What changing your injection day does to retatrutide exposure, and what it does not
What the pharmacokinetic data supports about dose timing, missed doses and interruption.
What happens when the drug is taken away: three randomised answers
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
Reading HbA1c in the presence of anaemia
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.
Escalating past the approved maximum, examined honestly
We looked at what the dose-ranging data supports about going higher, and it is thinner and less flattering than the market assumes.
Reading the receptor: what distinguishes cagrilintide from survodutide at the molecular level
A tour of what happens in the thirty seconds after binding, and why it matters at week thirty.
What SURMOUNT-1 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.
The one randomised trial that combined an incretin with supervised exercise
Mass and function are different endpoints and training affects them differently. Most coverage treats them as one.
Holding a dose is a decision, not a failure
A dose held long enough stops being a pause and becomes a maintenance decision. That transition is rarely made explicitly.
The trade has decided the ceiling is arbitrary. The trials disagree.
Where the curve flattens, what flattens with it, and what does not.
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.
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.
The supply gap as a clinical event
A supply interruption is a discontinuation with no notice, no taper and no plan. That is a distinct clinical situation.
Side effects, cost, supply, target: four reasons with four trajectories
A supply interruption is a discontinuation with no notice, no taper and no plan. That is a distinct clinical situation.
What the liraglutide schedule assumes about a person it has never met
The four-week step exists because four to five weeks is approximately how long a once-weekly drug takes to stop rising at a fixed dose. That is a good reason, and it is not…
A supply gap is a pharmacological event
The convention — resume lower, re-escalate — is not caution. It follows directly from the elimination half-life.
The skeleton responds to load, and load is falling
Density is a proxy for strength and an imperfect one, particularly when soft-tissue thickness over the measurement site is changing.
What happens when the drug is taken away: three randomised answers
What was withdrawn, from whom, after how long, and what was measured afterwards.
The arithmetic of a step: what doubling a dose actually asks of you
We work the arithmetic out in full, because it is arithmetic and it is short.
Thiamine and the vomiting patient
What the trials measured, which in the case of micronutrients is very little.