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ForumsOther Peptides & Research CompoundsSS-31 (Elamipretide) — my results so far Page 2

SS-31 (Elamipretide) — my results so far

Dr.RenalNash Tue, Sep 24, 2024 at 3:24 AM 18 replies 2,134 viewsPage 2 of 4
Dr.BariatricHTX
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Sep 25, 2024 at 7:00 AM#6
Dr.AddMedPHL said:
I want to add the drug interaction perspective on the pharmacology.

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.
3 23CarlaRPh_TPA, steph_laguna, fiona_glasgow
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stefan_berlin
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Berlin, DE
Sep 25, 2024 at 6:00 PM#7
Dr.RenalNash said:
Reading about receptor desensitisation and trying to work out which of the effects adapt over time and which do not, because people clearly experience…

Receptor pharmacology relevant to the pharmacology: semaglutide is a GLP-1R agonist with a C-18 fatty acid chain that enables albumin binding (>99%), creating a depot effect with a ~168-hour half-life enabling weekly dosing[1].

Tirzepatide is a dual GIP/GLP-1R agonist with higher GIP affinity (5:1 GIP:GLP-1 potency ratio). The GIP component may enhance beta-cell function and adipocyte lipid metabolism beyond what GLP-1 alone achieves.

For the pharmacology, the pharmacology explains the clinical differences between these agents.

References:
[1] Lau J, et al. J Med Chem. 2015;58(18):7370-7380.
2 22JessicaH_TX, KevinCompounds
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DebRD_ATL
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Atlanta, GA
Sep 26, 2024 at 5:00 AM#8
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…

PK/PD modeling for the pharmacology: understanding the pharmacokinetics helps optimize dosing. Semaglutide:

  • Tmax: 24-72 hours post-injection
  • T½: ~168 hours (7 days) — enables weekly dosing
  • Steady state: reached at 4-5 weeks
  • Bioavailability (SubQ): ~89%
  • Volume of distribution: ~12.5L (primarily plasma)

The albumin binding (>99%) is the key pharmacological innovation — creating a sustained-release effect from a single injection. Previous GLP-1 agonists (exenatide) required BID dosing due to rapid clearance.

1 21SleepDoc_PDX
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james_edin
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Sep 26, 2024 at 4:01 PM#9

A narrower follow-up, since the general answer is now clear:

What did you change at the same time, and can you separate the two now?

Last edited: Sep 26, 2024 at 6:01 PM
50 20oliver_london, tane_welly, Dr.PathRoch and 47 others
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Dr.RenalNash
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Sep 28, 2024 at 8:53 PM#10

OP back with an update, since a thread like this is useless without one.

Closing this out: the trough rather than the peak explains the pattern I was seeing on day six, which I had been blaming on the vial.

Last edited: Sep 29, 2024 at 1:53 AM
6 4maria_elpaso, anders_CPH, Dr.NutriCornell and 3 others
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