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ForumsOff-TopicNon-scale victories thread — anyone have experience?

Non-scale victories thread — anyone have experience?

greg_boulder Wed, Jun 26, 2024 at 8:05 AM 17 replies 2,242 viewsPage 1 of 4
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greg_boulder
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Jun 26, 2024 at 8:05 AM#1

Writing this once so I can stop repeating it across threads. It is about food noise, and it is deliberately narrow — everything I am not confident about is marked as such.

What is actually established

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.

The condition it depends on

It is worth naming the loss side of it. Food was a source of pleasure and structure, and its removal can leave a gap that people are not prepared for.

What I am not sure about

The bit I cannot resolve on my own is 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. Happy to be told the question itself is wrong.

— greg_boulder · corrections welcome and will be edited into this post with credit
34 4denise_HTX, raj_cambridge, ingrid_STO and 31 others
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TirzTom
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Jun 26, 2024 at 9:36 AM#2
greg_boulder said:
Food noise is the best term this community has produced and it describes something the trials did not measure well: the constant background…

The GLP-1 and alcohol use disorder connection, relevant to food noise: observational data from Scandinavian registries shows reduced alcohol-related hospitalizations in GLP-1 agonist users[1].

The mechanism is plausible: GLP-1R is expressed in the mesolimbic reward pathway (VTA, nucleus accumbens). Agonism at these receptors may reduce the reinforcing properties of alcohol, similar to the reduction in "food noise."

RCTs for GLP-1 agonists in AUD are now underway. If positive, this would be a paradigm-shifting repurposing of existing medications.

References:
[1] Wang W, et al. Nat Med. 2024;30:574-584.
Last edited: Jun 26, 2024 at 1:36 PM
33 3tom_AK, josh_phd_bmore, roxy_nash and 30 others
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labquiet_amy
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Jun 26, 2024 at 11:07 AM#3
greg_boulder 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.
32 2LibrarianMeg, bri_stats, pete_manc_UK and 29 others
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DebRD_ATL
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Jun 26, 2024 at 12:38 PM#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.

Last edited: Jun 26, 2024 at 4:38 PM
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gary_naperville
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Jun 26, 2024 at 9:29 PM#5
TirzTom said:
The GLP-1 and alcohol use disorder connection, relevant to food noise: observational data from Scandinavian registries shows reduced alcohol-related…

Adding a me-too, because a thread of one person's experience is not much use.

30 0RickReta_CO, PharmHunterJen, TomTeleRx and 27 others
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