After 14 days (2x the half-life), you'd be at roughly 25% of your steady-state peak level. That's getting low enough that you'd likely notice some return of appetite, and for T2D patients, some worsening of glycemic control.

The prescribing info says: if you miss a dose and the next scheduled dose is more than 2 days away, take the missed dose as soon as possible. If the next dose is within 2 days, skip the missed dose and take the next one on schedule.

If you've missed more than 2 consecutive weekly doses, there's a question of whether you need to re-titrate or can just resume at your current dose. Most prescribers say if you've missed 2 or fewer weeks, resume at the same dose. If you've missed 4+ weeks, consider starting back at a lower dose to avoid the nausea of "restarting" at a high dose with no steady-state buffer.

I accidentally went 16 days between doses once (the great Wegovy shortage of 2025 lol). The appetite came ROARING back around day 10-11. Food noise returned with a vengeance. It was honestly a useful experience because it reminded me how much the medication is actually doing.

When I got my next dose and resumed, the nausea came back for about 48 hours like I was starting a new dose level. So the re-titration concern is real if you miss multiple weeks.

Excellent pharmacology discussion. One additional nuance: the ~168-hour half-life applies to the TOTAL semaglutide (bound + unbound). Because semaglutide binds reversibly to albumin in the blood, the FREE (active) semaglutide concentration may fluctuate slightly differently than the total. However, at clinical doses, this distinction isn't practically important — the free fraction stays relatively constant because of the equilibrium dynamics.

For the OP's original question about optimizing timing: honestly, the best time to inject is whenever you'll REMEMBER to do it consistently. The PK is so forgiving that the #1 factor affecting efficacy is adherence, not timing optimization. Pick a day and time that fits your routine and stick to it. Set a phone alarm.

The only timing-related advice I give patients: if you experience injection-day nausea, try injecting in the evening so you sleep through the initial absorption phase. If you don't experience nausea, inject whenever is most convenient.

Fantastic thread. Summary for anyone finding this later:

• Semaglutide half-life is ~168 hours (7 days), making it one of the most pharmacokinetically forgiving weekly medications
• At steady state, plasma levels only fluctuate ~2x between peak and trough — very flat
• Being a day early or late is pharmacologically trivial
• Morning vs evening doesn't matter for efficacy, but may matter for side effect management
• Missing 2+ weeks may require a discussion with your provider about re-titration
• The most important timing factor is CONSISTENCY — pick a day and set a reminder

Thanks to PK_nerd_phd especially for the actual numbers. This forum continues to be the best resource on the internet for GLP-1 information imo.

bookmarking this whole thread. I've been stressed about the days I inject late and now I feel way better about it. Knowledge is power 💪