Dr.AddMedPHL said:

Food noise is the best term this community has produced and it describes something the trials did not measure well: the constant background…

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.

Following on from Dr.SurgeonPGH — and this may be the naive question:

How long did you give it before you decided it was working?

jason_paloalto said:

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

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.

jason_paloalto said:

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

jason_paloalto said:

...regarding food noise mechanism of action...

To build on this — the mechanism is more complex than "it makes you less hungry." GLP-1 agonists:

1. Activate hypothalamic satiety centers (appetite reduction)
2. Delay gastric emptying (prolonged fullness)
3. Potentiate glucose-dependent insulin secretion
4. Suppress glucagon secretion
5. Modulate reward pathway dopaminergic signaling
6. Reduce hepatic lipogenesis
7. Have direct cardiovascular protective effects

It's a multi-target drug with systemic metabolic effects. Understanding the mechanism helps us predict and manage side effects.

JenPlateau said:

Phantom hunger vs real hunger on food noise: learning to distinguish between the two has been a revelation.

"Food aversion" side effect of food noise that I wasn't prepared for: I used to LOVE cooking and trying new restaurants. Now certain foods — especially heavy cream sauces — literally repulse me.

It's not just reduced appetite; it's an active disgust response. My therapist says this is common and likely related to the reward pathway modulation. It's mostly a positive change, but I do miss enjoying food the way I used to.