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Evidence-based GLP-1 & peptide discussion since 2023
ForumsOff-TopicI fit into my college jeans and I am not okay (happy tears) — my results so far

I fit into my college jeans and I am not okay (happy tears) — my results so far

VanRx_Mike Sat, Oct 19, 2024 at 4:43 AM 43 replies 2,235 viewsPage 1 of 9
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VanRx_Mike
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Oct 19, 2024 at 4:43 AM#1

This gets cited here weekly, usually second-hand, so it is worth setting out what it does and does not establish.

Food noise is the best term this community has produced and it describes something the trials did not measure well: the constant background computation about food that most people with obesity live with and most people without it do not believe exists. GLP-1 agonism reduces the salience of food cues in the reward pathway rather than simply reducing hunger, which is why the reported experience is silence rather than willpower. It is also why its return on dose reduction is the first thing people notice, well before the weight moves.

Where I think it is weakest: the follow-up is short relative to how long people actually take these drugs, so durability is an assumption here rather than a finding.

So the question, as narrowly as I can put it: whether the quiet is the same mechanism as the appetite suppression or a separate one, because they seem to come and go on different schedules. Numbers rather than impressions, if you have them.

Note on sourcing:
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
34 4Dr.LeslieOBGYN, MikeNYC_runner and 31 others
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PeptideChemSF
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Oct 19, 2024 at 4:48 AM#2
VanRx_Mike said:
Food noise is the best term this community has produced and it describes something the trials did not measure well: the constant background…

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.

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labquiet_amy
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Oct 19, 2024 at 4:53 AM#3
VanRx_Mike 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.

References:
[1] Secher A, et al. J Clin Invest. 2014;124(10):4473-4488.
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Dr.GastroMayo
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Oct 19, 2024 at 4:58 AM#4
labquiet_amy said:
Central vs peripheral GLP-1R signaling in food noise: elegant studies using brain-penetrant vs peripherally-restricted GLP-1 agonists show that ~80%…
labquiet_amy 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.

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ben_calgary
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Oct 19, 2024 at 5:25 AM#5
PeptideChemSF said:
Phantom hunger vs real hunger on food noise: learning to distinguish between the two has been a revelation.

This matches mine closely enough to be worth saying so out loud. Nothing to add that would improve it.

30 0NauseaFreeNow, SteveThurs, B12Beth and 27 others
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