u/Cheetotiki

I progressed up from 1.5 to 4 to 9 with zero side effects and minimal reduced food noise and appetite until the second week of 9mg. Then last week started on 25 and bam! Food noise and appetite completely gone, nausea for a day or so but quickly went away.

But I’ve had very sensitive tingly skin, arms and legs. Sort of like the flu but no other flu symptoms. I skipped the pill for a day and it went away by the next day. I then took the pill with just 15 minutes fasting (so from a previous post, 40-60% absorbed) and it came right back. Is this common? Does it go away over time? Crazy annoying. I’ll stick it out another week or two but if it’s still going on I might go back down to 9, which was sorta working. I’d fro the 25 every other day but the sensitive skin comes back each day I take it.

I've just started the 25mg after having near zero response (and no side effects) on 1.5, 4, and the first two weeks of 9. Finally saw some effects during the last two weeks of 9. 25 has kicked my ass, so the chemist (but not biochemist! Consult your physician and all that!) in me decided to dive a bit more into the public data. I had been waiting 2 hours after taking the pill before eating/drinking.

To reduce the side effects of 25 I first took a day off, then tried a 15 minute window (zero side effects), then a 30 (minimal side effects) - those worked far better than the 2 hours. So from the data, what is the bioavailability at each of those?

15 minutes: 0.4% bioavailability, so 40-60% of what would be absorbed at the recommended 30 minute window.

30 minutes (recommended): 0.8% bioavailability. This sounds tiny and is, but is far better than most prior attempts at peptide absorption. For comparison, aspirin is 80%, cyclosporine is 30%, insulin is 0% (hence no effective oral insulins).

120 minutes: 1.4%, so a 75% increase over the 30 minute window. Absorption plateaus after 120 minutes.

The biggest increase is from 15 to 30 minutes, hence that recommendation.

So if you want to try to throttle, titrate, or increase the effects (and side effects), playing with the 15, 30, 30+ times can work.

What I also found: there is a 137% variability in bioavailability between individuals, though this decreases to 33% with regular doses over two weeks as the 7 day half life smooths things out. The amount of water consumed with taking the pill also plays a large part, with a tiny sip being significantly more effective than the recommended 4oz or even more. And prior experience with a GLP-1 (Zepbound 2.5 in my case) doesn't change absorption but does change receptor sensitivity. All of this can explain the wide range of "no effect" to "1.5mg kicked my ass" we see on this forum.