The semaglutide 4-week dose-escalation interval is approximately 5 half-lives — long enough for the new dose to reach steady state before the next bump. Faster titration outruns clearance and stacks side effects.
FDA guidance on semaglutide recommends discontinuation ≥2 months before planned conception. That's roughly 9 half-lives — well past the 5% washout threshold. Long-half-life drugs are unforgiving here.
Short-half-life GH-releasers (Ipamorelin, GHRP-2) are dosed multiple times daily because the pulse — not the steady level — is therapeutic. Steady-state arithmetic doesn't fully describe them. Background on peptide pharmacology.
This uses linear (first-order) pharmacokinetics. Most drugs and peptides at therapeutic doses follow this. Saturable metabolism, deep-compartment redistribution, and protein-binding effects can deviate from the model — confirm with the drug's published PK data for high-stakes decisions.
Steady-state is when the rate of drug entering your body equals the rate leaving — so blood levels stop rising and stabilize at a predictable peak and trough. It takes roughly 4–5 half-lives of consistent dosing to reach steady-state. For a drug with a 24-hour half-life, that's 4–5 days. For semaglutide (~7-day half-life), it takes 4–5 weeks at a fixed dose before levels plateau.
By convention, '5 half-lives' is considered effectively cleared — about 96.9% gone. By 7 half-lives, it's >99% gone. So a drug with a 24-hour half-life is essentially cleared in 5 days. Note: this is for the parent compound; active metabolites may persist longer.
Side effects and efficacy both correlate with steady-state levels, not your first dose. That's why GLP-1 protocols escalate slowly — each titration step plateaus over 4–5 weeks. Changing dose before reaching steady-state means you haven't seen the full effect of the previous dose. The calculator above shows when you'll plateau on any given dose schedule.
Elimination half-life is purely pharmacokinetic — how fast plasma concentration falls by 50%. Biological half-life accounts for downstream effects that outlast plasma clearance (e.g., a peptide gone from blood in hours but binding receptors that take days to recycle). For dosing math, elimination half-life is what you use. For 'when do effects fade,' biological half-life matters too.
A common rule: dose interval ≈ 1 half-life keeps levels relatively stable. Dose interval > 2 half-lives produces large peak-to-trough swings. For a 7-day half-life drug like semaglutide, weekly dosing keeps levels smooth. For a 24-hour half-life, daily works; every other day produces a sawtooth pattern. The calculator above shows the projected peak/trough at any interval you set.
Because clearance follows first-order kinetics — each half-life removes 50% of what's left, not 50% of the original dose. So after 1 half-life you're at 50%, after 2 at 25%, after 3 at 12.5%, etc. To get below 1%, you need ~7 half-lives. This is why long-half-life drugs (rapamycin ~62 hours, semaglutide ~7 days) take weeks to fully clear once stopped.