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ForumsTirzepatide (Mounjaro / Zepbound)My appetite is literally gone is this normal at 10mg — November 2025 Page 2

My appetite is literally gone is this normal at 10mg — November 2025

PeptideSynthNJ Thu, May 30, 2024 at 7:10 AM 45 replies 2,266 viewsPage 2 of 9
Dr.ReproEndo
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May 30, 2024 at 3:02 PM#6
JessicaH_TX said:
Alcohol relationship change with food noise: I used to drink cocktails most nights.

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.
26 21mona_PHX, andrew_nyc, Dr.EndoEP and 23 others
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TirzTom
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May 30, 2024 at 6:08 PM#7
PeptideSynthNJ 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…

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.

Last edited: May 30, 2024 at 10:08 PM
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DebRD_ATL
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May 30, 2024 at 9:14 PM#8
Dr.ReproEndo said:
Central vs peripheral GLP-1R signaling in food noise: elegant studies using brain-penetrant vs peripherally-restricted GLP-1 agonists show that ~80%…

Rebound hunger after missed dose of food noise: I missed my injection by 3 days due to a shipping delay and the hunger came ROARING back. Like a switch flipped. It was eye-opening to feel the difference.

This experience actually reinforced my understanding of what the medication does — it's not just "suppressing appetite," it's normalizing dysregulated hunger signaling. When the drug wears off, you feel the full force of what it was managing.

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lisa_labSD
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May 31, 2024 at 12:20 AM#9

Following on from KristenIndy — and this may be the naive question:

Did your prescriber agree with that reading, and if not what was their objection?

Last edited: May 31, 2024 at 3:20 AM
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PeptideSynthNJ
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May 31, 2024 at 3:12 PM#10
DebRD_ATL said:
Rebound hunger after missed dose of food noise: I missed my injection by 3 days due to a shipping delay and the hunger came ROARING back.

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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