Semaglutide PK modeling — when to time your injection

That's an excellent lay explanation and you've got the key concepts right. Let me add some precision.

The accumulation ratio for a drug given at intervals equal to its half-life is approximately 2:1. This means at steady state, your average plasma concentration is about twice what it would be from a single dose. Your peak-to-trough ratio of 1.5–2:1 is correct for once-weekly dosing.

Here's a concrete example. If you take 1.0mg weekly:

• Week 1: After injection, peak ~1.0 dose-equivalents. By end of week, ~0.5 remains.
• Week 2: You inject 1.0 on top of 0.5 remaining. Peak ~1.5. End of week ~0.75 remains.
• Week 3: Inject on top of 0.75. Peak ~1.75. End of week ~0.875.
• Week 4: Inject on top of 0.875. Peak ~1.875. End of week ~0.9375.
• Week 5 (≈ steady state): Inject on top of ~0.94. Peak ~1.94. End of week ~0.97.

You can see how the levels plateau. At steady state, you're oscillating between roughly 1 and 2 dose-equivalents. The drug never fully leaves, which is exactly what makes once-weekly dosing feasible.

Practical implication #1: If you stop taking semaglutide, it doesn't leave your system in one week. It takes 5–7 half-lives (5–7 weeks) for the drug to be essentially eliminated. This is why appetite changes can linger for over a month after the last dose.

Practical implication #2: Don't judge a new dose after one week. You haven't reached steady state. Give it the full 4–5 weeks.

^[1] Marbury TC, et al. "Pharmacokinetics and Tolerability of a Single Dose of Semaglutide, a Human Glucagon-Like Peptide-1 Analog, in Subjects With and Without Renal Impairment." Clin Pharmacokinet. 2017;56(11):1381-1390.

Previously posted:

If you stop taking semaglutide, it doesn't leave your system in one week. It takes 5–7 half-lives (5–7 weeks) for the drug to be essentially eliminated.

This is the thing that surprised me most when I learned about it. I panicked once when I missed a dose because I thought the drug would be "gone." But at steady state, missing one dose barely makes a dent. Your levels drop from maybe 2 units to 1.5 units — you still have MORE drug in your system than you did after your very first injection.

The long half-life is a feature, not a bug. It's what makes this drug so forgiving of the occasional missed or late dose.

So wait... when people say they feel the drug "wearing off" on day 6 or 7 of their weekly cycle, is that real or in their head? Because based on what you're saying, the levels barely drop during a single week.

It's probably a combination. At steady state, the trough level is about 50–65% of the peak. So there IS a measurable decline within each weekly cycle. Whether that 35–50% decline is enough to produce noticeable symptom changes is highly individual. Some people are sensitive to that fluctuation. Others aren't.

There's also a psychological component — if you know your injection day is tomorrow, you might be more attuned to hunger signals. The drug is absolutely still active at trough, just not at its maximum effect.