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ForumsTirzepatide (Mounjaro / Zepbound)My appetite is literally gone is this normal at 10mg Page 2

My appetite is literally gone is this normal at 10mg

robert_kc Mon, Mar 23, 2026 at 9:12 PM 12 replies 727 viewsPage 2 of 3
DataDave
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Mar 24, 2026 at 5:36 PM#6
LarryQC_SD said:
Neuroscience perspective on food noise: GLP-1 receptors are expressed throughout the CNS, with high density in the hypothalamic arcuate nucleus, area…

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.
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Dr.PeteFamMed
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Mar 25, 2026 at 1:42 AM#7
robert_kc 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.

References:
[1] Secher A, et al. J Clin Invest. 2014;124(10):4473-4488.
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paige_pharma
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Mar 25, 2026 at 9:49 AM#8
DataDave said:
The GLP-1 and alcohol use disorder connection, relevant to food noise: observational data from Scandinavian registries shows reduced alcohol-related…

Alcohol relationship change with food noise: I used to drink 3-4 beers most nights. Since starting GLP-1 therapy, I have zero interest in alcohol. Haven't had a drink in 9 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 $223/month on alcohol. Triple win.

Last edited: Mar 25, 2026 at 10:49 AM
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emma_london
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Mar 25, 2026 at 5:56 PM#9

One thing that is still open after claudia_zurich’s answer:

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

Last edited: Mar 25, 2026 at 11:56 PM
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robert_kc
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Mar 27, 2026 at 8:53 AM#10
paige_pharma said:
Alcohol relationship change with food noise: I used to drink 3-4 beers most nights.
paige_pharma 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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