[Discussion] we use "appetite suppression" to describe three different mechanisms
we use "appetite suppression" to describe three different mechanisms. It is the sort of thing everyone half-believes and nobody writes down.
Started reading limitations sections first. It has changed how much weight I give to almost everything posted here.
Asked a question here that I thought was stupid and got three papers back. Best thread I have been in on this site.
The mental model, in four steps, that makes the rest of this site legible.
One: gut hormones amplify the insulin response to food. Two: agonists at those receptors act peripherally on insulin secretion and gastric emptying, and centrally on appetite. Three: structural modification gives them a long half-life, so exposure is smooth and weekly. Four: tolerance develops to some effects and not to others.
From those four, most of what the experience boards report falls out: why the side effects cluster early, why they settle at a stable dose, why appetite reduction persists, and why the scale and the appetite move on different clocks.
If two or three other people have done the same thing we might actually learn something. Alone it is an anecdote.
best — the order this archive was captured in
Are we talking about receptor affinity or clinical potency?
Was completely wrong about the gastric emptying story in a thread here two years ago. Someone corrected me with a citation and I have not made that mistake since.
What was the exposure in that experiment relative to therapeutic?
receptor agonism is not the same as receptor activation in every tissue
Does the effect persist with continued dosing or does tolerance develop?
Is there any human data on that mechanism yet?
Why mechanism talk keeps misleading people, including me.
A mechanism tells you a direction. It does not tell you a magnitude, a timescale, or whether the pathway is operative at the exposures involved. "Receptor X is expressed in tissue Y" is a fact; "therefore effect Z in a person" is a hypothesis with several missing steps.
The corrective is boring and it works: ask whether the evidence is preclinical or human, ask what exposure was used, and read the limitations section before the abstract. Most of the confidently wrong posts on this board — several of them mine — skipped all three.
Which receptor arm are you attributing that to?
The half-life explanation was the thing that made weekly dosing intuitive for me rather than arbitrary.
Retitled to distinguish preclinical from clinical, which the original ran together.
Push back: a receptor being expressed in a tissue does not tell you the agonist reaches it at therapeutic exposure.
I would not read that in vitro number across to a person. The conditions are nothing like physiological.
Do you have the paper, or a summary of it?
GIP is the arm people argue about because the biology is genuinely unsettled
read the discussion section, that is where the honesty lives
Disagree. That is a preclinical finding in a rodent model and you are stating it as human pharmacology.
- 1Why mechanism talk keeps misleading people, including me. A mechanism tells…9 comments in this branch · started by u/employer_carveout
- 2Are we talking about receptor affinity or clinical potency?6 comments in this branch · started by u/second_week_sceptic