Short answer first, then the reasoning. 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.
My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
What I am trying to establish is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.
Numbers rather than impressions, if you have them.
mike_nyc said:The pharmacokinetics explain nearly every practical question asked here.
Agreed, and the adaptation point cuts both ways: tachyphylaxis to gastric emptying is why tolerability improves, and it is also why people who were relying on physical fullness feel the effect fade while the appetite effect is still working.
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Browse GL BiochemZaraB_AL said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
Same experience, arrived at from the opposite direction.
Adding the clinical framing, because it changes how the question reads.
Anti-inflammatory mechanisms of GLP-1 agonists and cardiovascular risk: beyond weight loss, GLP-1R activation directly suppresses NF-κB signaling, reduces NLRP3 inflammasome activation, and decreases monocyte/macrophage adhesion to endothelium[1].
Clinical correlates: hsCRP reduction of 30-60% (consistently seen across trials), reduced carotid intima-media thickness, and decreased coronary plaque inflammation on PET imaging.
These anti-inflammatory effects likely contribute to the cardiovascular benefit seen in SELECT — and may explain benefits beyond what weight loss alone would predict.
[1] Hogan AE, et al. Diabetologia. 2014;57(4):781-784.