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ForumsOff-TopicWhat does your shot day routine look like? — my results so far

What does your shot day routine look like? — my results so far

stefan_berlin Tue, Jul 9, 2024 at 2:19 PM 32 replies 2,086 viewsPage 1 of 7
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stefan_berlin
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Jul 9, 2024 at 2:19 PM#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. Practical detail welcome, however dull — the duller the better.

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.
48 18NeuroNate, JessicaH_TX, KevinCompounds and 45 others
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TrialNerd_Beth
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Jul 9, 2024 at 2:33 PM#2
stefan_berlin 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.
Last edited: Jul 9, 2024 at 6:33 PM
47 17PharmHunterJen, TomTeleRx, DoseLogDan and 44 others
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Dr.NateNeph
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Jul 9, 2024 at 2:47 PM#3
stefan_berlin said:
Food noise is the best term this community has produced and it describes something the trials did not measure well: the constant background…

"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 fried foods — 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.

46 16SteveThurs, B12Beth, RickReta_CO and 43 others
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lisa_labSD
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Jul 9, 2024 at 3:01 PM#4
Dr.NateNeph said:
"Food aversion" side effect of food noise that I wasn't prepared for: I used to LOVE cooking and trying new restaurants.

Alcohol relationship change with food noise: I used to drink 2 glasses of wine most nights. Since starting GLP-1 therapy, I have zero interest in alcohol. Haven't had a drink in 5 months.

The "food noise" reduction seems to extend to other reward-seeking behaviors, including alcohol. My liver enzymes have improved, my sleep is better, and I've saved roughly $243/month on alcohol. Triple win.

45 15lori_vegas, Dr.PulmRoch, maya_sedona and 42 others
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carl_compliance
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Jul 9, 2024 at 4:13 PM#5
TrialNerd_Beth said:
Central vs peripheral GLP-1R signaling in food noise: elegant studies using brain-penetrant vs peripherally-restricted GLP-1 agonists show that ~80%…

This matches mine closely enough to be worth saying so out loud. The detail I would add is minor and it is already implied above.

44 14dave_SLC, FDA_TrackerJim, ricardo_MIA and 41 others
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