Has anyone tried splitting their weekly semaglutide dose into two injections? For example, instead of 1.0mg once per week, doing 0.5mg every 3.5 days?

My thinking: the drug has a 168-hour half-life, so there IS some fluctuation between peak and trough within a week. If I split the dose, I'd theoretically have more stable plasma levels with less peak-to-trough variation. This might mean more consistent appetite suppression and potentially fewer side effects from the peak.

Am I wrong about the pharmacology here? Has anyone actually tried this?

Your pharmacokinetic reasoning is actually sound. With a 168-hour half-life, the peak-to-trough ratio at steady state with once-weekly dosing is approximately 1.5:1 to 2:1. Splitting to twice weekly would reduce this ratio, giving flatter, more consistent levels.

However, there are several important considerations:

1. The clinical trials were all conducted with once-weekly dosing. We have no RCT data on split dosing. The efficacy and safety profile we rely on is based on once-weekly administration.
2. The GI side effects may actually be mediated more by local GI receptor activation than by plasma levels. Each injection causes a bolus of drug to reach GI receptors. Two smaller boluses might or might not be better tolerated than one larger one — we genuinely don't know.
3. Practical downsides: Twice the injections, twice the injection site management, harder to maintain a consistent schedule, and if you're using compounded product, more frequent vial punctures which marginally increases contamination risk.

That said, some clinicians do prescribe split dosing for patients who experience late-week "wearing off" or who have severe peak-related nausea. It's off-label but not unreasonable.

Thanks for explaining that. I'm specifically noticing that days 5–7 after my injection, my appetite starts creeping back noticeably. By the morning of my injection day, I'm ravenous. That's what got me thinking about splitting.

Previously posted:

I'm specifically noticing that days 5–7 after my injection, my appetite starts creeping back noticeably.

This is EXACTLY why I split my dose. I was at 1.7mg once weekly and days 5–7 were brutal — the appetite came roaring back and I'd overeat, then feel terrible when I took my next dose and the nausea hit.

I switched to 0.85mg every 3.5 days (Sunday evening and Thursday morning) and the difference was night and day. Much more even appetite suppression throughout the week. No more "feast and famine" cycle. My total weekly dose is exactly the same, just distributed differently.

I discussed it with my provider first and she was supportive. She said she has several patients doing this.

I want to point out that the "wearing off" phenomenon may also be addressable by increasing the dose rather than splitting it. If you're at 1.0mg and appetite returns by day 5, it's possible you simply need 1.7mg. Higher doses produce higher trough levels, which might solve the problem without the complexity of split dosing.

Of course, higher doses also mean higher peak levels and potentially more side effects, so there's a tradeoff. But it's worth considering before adding complexity to your regimen.