Off-Cycle
Also known as: washout period · rest phase
Off-cycle is the planned break in a cycle when you stop taking a compound, used to let the drug clear and to see which effects last.
Off-cycle is the period after the last dose of an on-cycle and before the next one starts. In the first part of it, the compound is still in your body. Drug levels fall by half with each half-life, so it takes roughly 4 to 5 half-lives before most of it is gone (1 − 0.5^4 = 94%; 1 − 0.5^5 = 97%). For a long-acting drug that is a long time: the Wegovy label notes that with a half-life of about 1 week, semaglutide will be present in the circulation for about 5 to 7 weeks after the last 2.4 mg dose.
Two things are supposed to happen off-cycle: the compound clears, and any tolerance that built up during the on-cycle may reverse. The second part is compound-specific. In one 16-week study of twice-daily hexarelin, the blunted growth hormone response had recovered to baseline 4 weeks after stopping. For most research peptides, nobody has measured whether, or how fast, any recovery happens.
Why it matters
The off-cycle tells you which effects depended on the compound. If a result fades after the drug has cleared, it needed continued exposure. That is what was seen when semaglutide 2.4 mg and lifestyle support were stopped after 68 weeks in the STEP 1 trial extension: participants regained about two-thirds of their prior weight loss within a year, and most cardiometabolic improvements moved back toward baseline.
That makes an off-cycle a decision with costs, not a neutral pause. For a compound whose benefit depends on ongoing exposure, a break means losing some or all of that benefit. For a compound with documented tolerance, a break may restore the response. Know which kind you are dealing with before you plan one.
How to set off-cycle length
- Find the elimination half-life of each compound you were taking, ideally from a prescribing label or a human pharmacokinetic study.
- Take the longest one and multiply by 5 to estimate when about 97% has been eliminated. The half-life decay tool (/tools/half-life-decay) plots this curve for you.
- Schedule any "off" labs after that point if you want values that are not influenced by remaining drug.
- If the reason for the break is tolerance, check whether recovery has actually been measured for that compound. If it has not, the off-cycle length is a guess.
Minimum washout ≈ 5 × elimination half-life (about 97% eliminated)
Semaglutide's half-life is about 1 week, so 5 half-lives is about 5 weeks (1 − 0.5^5 = 0.969, about 97% eliminated). That lines up with the label's statement that semaglutide remains in circulation for about 5 to 7 weeks after the last dose.
Common mistakes
- Drawing "off-cycle" bloodwork a few days after the last dose of a long-acting compound, while most of it is still circulating.
- Assuming a break automatically resets receptor sensitivity without evidence for that compound.
- Reading weight or symptom rebound after stopping as a withdrawal side effect, when it may simply be the loss of the drug's effect.
- Using the same off-cycle length for every compound regardless of half-life.
Sources
- Prescribing informationWEGOVY (semaglutide) injection, for subcutaneous use: Prescribing Information. U.S. Food and Drug Administration, 2021.
- Clinical trialGrowth hormone status during long-term hexarelin therapy. J Clin Endocrinol Metab, 1998. PMID 9589671.
- Clinical trialWeight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab, 2022. PMID 35441470.
Page updated . How we grade evidence: methodology.
Related Terms
On-Cycle
On-cycle is the phase of a cycle when you are actively taking a compound, as opposed to the planned break (off-cycle).
Cycle
A cycle is a planned period of taking a compound followed by a planned break, often repeated over time.
Receptor Desensitization
Receptor desensitization is the drop in a cell's response to a drug or hormone after repeated or continuous stimulation of its receptor.
Half-Life
Half-life (t½) is the time it takes for the concentration of a drug in your blood plasma to fall by half.
Look up any peptide term inside DoseCraft Pro
The glossary is just the start. Inside DoseCraft you get 90+ compound deep-dives, a PK-aware protocol engine, interaction checker, and vendor trust scores — every term surfaced in protocol-design context, not a separate page.
Start Free Trial