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ForumsOther Peptides & Research CompoundsBPC-157 systemic vs local effects — September 2026

BPC-157 systemic vs local effects — September 2026

SleepFixSam Fri, Oct 18, 2024 at 7:05 PM 35 replies 2,053 viewsPage 1 of 7
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SleepFixSam
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Oct 18, 2024 at 7:05 PM#1

Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using it.

The mechanism is more central than most summaries suggest. Receptor agonism in the arcuate nucleus activates POMC neurons and inhibits AgRP/NPY signalling, and the downstream MC4R pathway is the same one disrupted in monogenic obesity — convergent genetic evidence that the target is the right one. Peripherally there is glucose-dependent insulin secretion, glucagon suppression and delayed gastric emptying, but the gastric component largely adapts over months while the central effect persists, which is why the durable effect is appetite rather than fullness.

Where I think it is weakest: the population was selected and supported in ways a real cohort is not, so I would read the effect size as a ceiling rather than an expectation.

So the question, as narrowly as I can put it: which effects tachyphylax and which persist, because the answer explains why tolerability improves while the appetite effect keeps working. I have searched first, so if this is covered somewhere point me at it and I will read it.

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 18pete_nash, hank_denver, carlos_SATX and 45 others
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Dr.BariatricHTX
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Oct 18, 2024 at 7:49 PM#2
SleepFixSam said:
The mechanism is more central than most summaries suggest.

Amycretin (AMY/GLP-1 dual agonist) emerging data relevant to the pharmacology: Phase 1 showed -13.1% body weight at only 12 weeks, the fastest trajectory ever seen for an anti-obesity agent[1].

Amylin receptor agonism enhances satiety signaling through the area postrema and reduces glucagon secretion. Combined with GLP-1R agonism, this dual mechanism may produce even greater efficacy than current agents.

Early-stage data — interpret with caution. But the trajectory is extraordinary.

References:
[1] Novo Nordisk investor presentation, September 2023.
Last edited: Oct 19, 2024 at 1:49 AM
47 17pete_RVA, CarlaRPh_TPA, steph_laguna and 44 others
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kate.chem
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Oct 18, 2024 at 8:33 PM#3
SleepFixSam said:
The mechanism is more central than most summaries suggest.

Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. The pharmacokinetics explain nearly every practical question asked here. Albumin binding above 99% slows clearance enough to make weekly dosing possible; a terminal half-life near a week means four to five weeks to steady state and therefore a four-week titration interval; subcutaneous bioavailability around 89% means injection site barely matters. Those three facts answer most timing questions before they are asked.

46 16tyler_CSCS, VanRx_Mike, steve_okc and 43 others
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VanRx_Mike
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Oct 18, 2024 at 9:17 PM#4
kate.chem said:
The pharmacokinetics explain nearly every practical question asked here.

Semaglutide structural biology relevant to the pharmacology: semaglutide is a 31-amino acid peptide with 94% homology to native GLP-1(7-36). Three key modifications enable its pharmacokinetic profile:

  1. Aib8 substitution: DPP-4 resistance (prevents enzymatic degradation)
  2. Arg34 substitution: improved chemical stability
  3. C18 fatty diacid at Lys26: albumin binding → long half-life

These three modifications transform a peptide with a 2-minute half-life (native GLP-1) into one with a 168-hour half-life (semaglutide). A masterclass in peptide engineering.

45 15Dr.Martinez, mike_mod, SarahChen_PharmD and 42 others
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mark_tokyo
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Oct 19, 2024 at 1:24 AM#5
Dr.BariatricHTX said:
Amycretin (AMY/GLP-1 dual agonist) emerging data relevant to the pharmacology: Phase 1 showed -13.1% body weight at only 12 weeks, the fastest…

Can confirm. Same sequence, different timescale. Posting only so the count is not one.

44 14TrialNerd_Beth, HPLC_Greg, LibrarianMeg and 41 others
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