TB-500 for tissue repair — 12 month update

KristenIndy 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…

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.

Dr.GastroMayo said:

Receptor pharmacology relevant to the pharmacology: semaglutide is a GLP-1R agonist with a C-18 fatty acid chain that enables albumin binding (>99%),…

Dr.GastroMayo has the substance of this right. The condition it depends on is worth stating. 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.

KristenIndy 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.

Adding the clinical framing, because it changes how the question reads.

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.