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.
Delphine Ruzek
Page 2 of 7 of this archive, newest first.
Archive — page 2
121 piecesThe interventions with trial support, and the much longer list without
Constipation is the most tractable of the effects and the most consistently under-managed.
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.
The trade has decided the ceiling is arbitrary. The trials disagree.
Where the curve flattens, what flattens with it, and what does not.
A mass on a WWB certificate is a beginning, not a conclusion
What a single-stage mass measurement supports, what it excludes, and the gap between the two.
Tandem mass spectrometry, and the difference between weighing and reading
An intact mass measurement establishes elemental composition, at best. The number of distinct sequences consistent with a given composition is astronomically large.
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 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.
The mechanism behind the mechanism
The clinical effect profile is almost fully predictable from where the receptor is expressed, which is unusual and useful.
Residual stomach content on endoscopy: the studies
Holding a dose before a procedure has a kinetic problem: a weekly drug with a seven-day half-life cannot be cleared by skipping one injection.
Mapping a rotation that you will actually follow
The evidence base here is the insulin injection-technique literature, which is large and transfers well on tissue questions.
The eighteenth month, and the conversation that should have happened in the third
Two withdrawal-design trials tell us what happens when treatment stops. Neither tells us what the lowest effective maintenance dose is.
Do you need the top of the ladder?
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
How a single percentage came to stand for quality
This piece takes the measurement apart into the decisions it is made of, because each decision moves the answer.
Delayed emptying explains some of this, and not all of it
The receptor populations that produce satiety and the ones that produce nausea overlap substantially. That is why the ceiling of this drug class is where it is, and it is…
Why VendorInvestigate may run electrospray where another laboratory runs MALDI
The two ionisation techniques in general use produce different charge distributions, different adducts and different failure modes. Certificates almost never say which was…
Delayed emptying explains some of this, and not all of it
The receptor populations that produce satiety and the ones that produce nausea overlap substantially. That is why the ceiling of this drug class is where it is, and it is…
The glucagon receptor arm, and why it is the hardest to reason about
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.
Why purity is the cheapest number to flatter
Peptide content, identity, aggregate burden, moisture and endotoxin are all more informative for some purposes. All of them cost more.
Attribution is the hard part
Rapid weight loss by any means raises gallstone risk. Separating that from a direct drug effect requires a comparator, and the trials have one.