The limits of mechanism: why receptor data will not tell you who responds
A catalogue of open questions, with an assessment of how likely each is to be resolved.
Cagrilintide
Page 2 of 4 of this archive, newest first.
The limits of mechanism: why receptor data will not tell you who responds
A catalogue of open questions, with an assessment of how likely each is to be resolved.
What the GLP-1 receptor actually does when liraglutide binds it
The receptor is expressed in more tissues than the popular account allows, and that is the whole story.
What the GLP-1 receptor actually does when orforglipron binds it
The class is described as though every molecule in it did the same thing. At the receptor, they demonstrably do not.
What the GLP-1 receptor actually does when survodutide binds it
The receptor is expressed in more tissues than the popular account allows, and that is the whole story.
What the GIP receptor adds: reading orforglipron as two drugs in one sequence
The glucagon arm raises energy expenditure and also raises hepatic glucose output. Balancing those is the whole engineering problem.
Three receptors, one peptide: the design problem behind triple agonism
What adding GIP activity does, on the current evidence, and what remains unresolved.
Is liraglutide better than mazdutide, or differently balanced?
What adding GIP activity does, on the current evidence, and what remains unresolved.
From cell to clinic: where the extrapolation stops being safe
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
From cell to clinic: where the extrapolation stops being safe
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
From cell to clinic: where the extrapolation stops being safe
The mechanism is well described. The variance is not.
Vagal afferents, the area postrema, and the anatomy of nausea
A tour of the tissues where the receptor is expressed, and what happens in each.
The incretin receptors, ranked by how much we actually know about them
Selectivity, potency and efficacy are three different measurements. The trade routinely reports none of them.
The limits of mechanism: why receptor data will not tell you who responds
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
Three receptors, one peptide: the design problem behind triple agonism
Head-to-head data exists for some of these comparisons and not for others. This piece says which.
The limits of mechanism: why receptor data will not tell you who responds
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
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.
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.
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.
The glucagon receptor arm, and why it is the hardest to reason about
What adding GIP activity does, on the current evidence, and what remains unresolved.