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ForumsOther Peptides & Research CompoundsHas anyone dealt with are any of these other peptides actually backed by science?

Has anyone dealt with are any of these other peptides actually backed by science?

kevin_tulsa Thu, May 16, 2024 at 9:49 AM 13 replies 2,041 viewsPage 1 of 3
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kevin_tulsa
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May 16, 2024 at 9:49 AM#1

I went looking for why the dosing schedule is what it is and found that almost every practical question on this board has a pharmacokinetic answer nobody states.

The narrow version of the question is which effects tachyphylax and which persist, because the answer explains why tolerability improves while the appetite effect keeps working.

Numbers rather than impressions, if you have them.

24 19fiona_glasgow, Dr.RheumBOS, greg_boulder and 21 others
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anders_CPH
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May 16, 2024 at 10:03 AM#2
kevin_tulsa said:
I went looking for why the dosing schedule is what it is and found that almost every practical question on this board has a pharmacokinetic answer…

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.
23 18MariaRD, AussieAnna, BethLabQueen and 20 others
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InsuranceTom
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May 16, 2024 at 10:17 AM#3
anders_CPH 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…

That is correct as far as it goes, and here is where it stops going. 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.

Last edited: May 16, 2024 at 3:17 PM
22 17Dr.ReproEndo, lucas_SP_BR, lisa_labSD and 19 others
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Dr.DermMIA
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May 16, 2024 at 10:31 AM#4
kevin_tulsa said:
I went looking for why the dosing schedule is what it is and found that almost every practical question on this board has a pharmacokinetic answer…

Second this. I had assumed I was the exception until I read this.

Last edited: May 16, 2024 at 12:31 PM
21 16PeptideChemSF, A1cHero_PHX, Dr.RenalNash and 18 others
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anna.melb_AU
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May 16, 2024 at 11:45 AM#5

Clinical perspective, offered as context rather than as advice.

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.

20 15Dr.LipidDallas, alex_tucson, kevin_tulsa and 17 others
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