What the GIP receptor adds: reading cagrilintide as two drugs in one sequence
Head-to-head data exists for some of these comparisons and not for others. This piece says which.
Retatrutide
An investigational triple GIP/GLP-1/glucagon receptor agonist in the TRIUMPH programme.
Where the receptor is: a tissue-by-tissue account of liraglutide’s reach
The central effects are not a bonus. On the current evidence they are the principal mechanism of weight loss.
Why a drug that acts on the pancreas changes what food tastes like
Receptor expression maps explain the effect profile better than any dose-response curve.
Gastric emptying is a mechanism, not a side effect
The central effects are not a bonus. On the current evidence they are the principal mechanism of weight loss.
One receptor, several signals: the case for reading liraglutide as a biased agonist
Receptor pharmacology explains more of the clinical picture than the dose does — and almost none of it appears in the material patients are given.
One receptor, several signals: the case for reading semaglutide as a biased agonist
A tour of what happens in the thirty seconds after binding, and why it matters at week thirty.
How a peptide that lasts seven days binds a receptor that recycles in minutes
What the in-vitro data supports, what it does not, and where the extrapolation to a person begins.
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.
Reading the receptor: what distinguishes survodutide from liraglutide at the molecular level
Receptor pharmacology explains more of the clinical picture than the dose does — and almost none of it appears in the material patients are given.
Beta-arrestin, cAMP, and the part of dulaglutide’s mechanism nobody quotes
The receptor is expressed in more tissues than the popular account allows, and that is the whole story.
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.
Why the fifth week of a semaglutide dose feels different from the first
An accumulation model, drawn from published parameters, with its assumptions stated.
Dual, triple, co-formulated: a taxonomy the coverage keeps collapsing
Head-to-head data exists for some of these comparisons and not for others. This piece says which.
Why the fifth week of a mazdutide dose feels different from the first
The exposure curve explains the timing of both the benefit and the side effects. It is almost never shown to the person injecting.
Vagal afferents, the area postrema, and the anatomy of nausea
Receptor expression maps explain the effect profile better than any dose-response curve.
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 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.
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.