This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
Coming back to post #89, because the follow-up matters more than the original answer.
GLP-1 receptor signalling: the GLP-1 receptor is expressed on beta cells (insulin secretion), on neurons (appetite and gastric motility), and on myocardium (contractility). Different tissues respond to the same signal in different ways.
Picking up post #89: that is the part I would want checked first.
Long-term receptor changes: very little is known about what happens to receptor expression, signalling, and downstream effects over years of exposure to these compounds. That is exactly the knowledge gap phase 3 trials exist to fill.
GIP receptor signalling: the glucose-dependent insulinotropic peptide receptor (GIP) is involved in glucose-stimulated insulin secretion. GIP agonism is thought to contribute to tirzepatide's effect but the mechanism is not fully settled.
Glucagon receptor agonism: glucagon receptor agonism increases energy expenditure and promotes hepatic fat oxidation. The mechanism is distinct from GLP-1 and GIP agonism and the clinical consequences are still being characterised.
This follows post #93 rather than contradicting it.
I disagree with the reply above, and I think the disagreement is substantive rather than terminological.
The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.
Bias and desensitisation: receptors can be biased (preferentially activating some downstream pathways over others) and can desensitise over time (responding less to the same stimulus with repeated exposure). Both might affect long-term response to these compounds.
Central versus peripheral action: GLP-1 agonism works through both central nervous system effects (appetite) and peripheral effects (gastric motility, insulin). The balance is not fully characterised.
Species differences: rodent studies show the same compounds produce effects in rodents that predict human effects reasonably well for semaglutide and tirzepatide. The track record is less clear for novel compounds with less human data.
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