Dr.GastroMayo said:

The thing that changed for me was not hunger, it was that the constant background negotiation about food simply stopped, and I had not realised it was…

Central vs peripheral GLP-1R signaling in food noise: elegant studies using brain-penetrant vs peripherally-restricted GLP-1 agonists show that ~80% of the weight loss effect is centrally mediated[1].

The key brain regions: arcuate nucleus (appetite), area postrema (nausea), NTS (satiety), VTA/NAc (reward). Peripheral effects (gastric emptying, insulin secretion) contribute but are secondary for weight loss.

This has implications for next-gen drugs: optimizing brain penetration and CNS receptor occupancy may be more important than systemic exposure.

HPLC_Greg said:

Central vs peripheral GLP-1R signaling in food noise: elegant studies using brain-penetrant vs peripherally-restricted GLP-1 agonists show that ~80%…

Rebound hunger after missed dose of food noise: I missed my injection by 3 days due to a shipping delay and the hunger came ROARING back. Like a switch flipped. It was eye-opening to feel the difference.

This experience actually reinforced my understanding of what the medication does — it's not just "suppressing appetite," it's normalizing dysregulated hunger signaling. When the drug wears off, you feel the full force of what it was managing.

Dr.GastroMayo said:

The thing that changed for me was not hunger, it was that the constant background negotiation about food simply stopped, and I had not realised it was…

This matches mine closely enough to be worth saying so out loud.

From the other side of the consultation, briefly.

Phantom hunger vs real hunger on food noise: learning to distinguish between the two has been a revelation. Real hunger: gradual onset, physical stomach sensation, any food sounds good. Phantom hunger: sudden, emotionally triggered, specific food cravings, occurs right after eating.

The GLP-1 agonist suppresses real hunger beautifully. Phantom hunger still pops up but I can now recognize it for what it is — an emotional signal, not a physical need. Mindfulness training helped enormously with this distinction.