Four weeks on, two weeks off did not come from a trial.

Cycling, as a word and as a practice, comes from anabolic steroid use: a period of administration followed by a deliberate break, built around concerns specific to exogenous androgens, chiefly that the body's own testosterone production shuts down and needs time, or a separate drug protocol, to recover. That is a real, measured phenomenon in that class of compound.

Peptides are a different class of molecule acting through different receptors, and the on/off ratios that circulate for them, four weeks on and two off, eight weeks on and four off, twelve on and four off, are the same arithmetic carried over by habit rather than by evidence. A number that is correct for suppressing the hypothalamic-pituitary-gonadal axis is not automatically correct for a growth hormone secretagogue, a tissue repair fragment, or a GLP-1 receptor agonist, and nothing about the arithmetic checks whether it transfers.

That does not make every cycling instinct wrong. It makes it unproven until shown otherwise, which is a different thing, and the rest of this page sorts out where the difference actually lands.

Growth hormone release from the pituitary is a machine with a governor: GHRH turns it on, somatostatin turns it off, and the pulses that result are the point, not a side effect. Feed that machine a constant, unbroken signal instead of pulses and researchers have repeatedly asked whether the pituitary keeps responding at full strength. The honest answer, across five human studies run by the same Virginia group in the 1980s plus one Dutch trial a decade later, is: it depends on how the signal is delivered, and it has been measured well enough to say so precisely rather than in slogans.

Put those studies next to each other honestly and the finding is not “GH secretagogues need to be cycled” or “they don't.” It is narrower and more useful: receptor desensitization to continuous GHRH stimulation is a real, measured phenomenon at the hours-to-days timescale in small human studies, it does not show up cleanly at 24 hours or reliably at 14 days in the same research group's own hands, and nobody has run the study that would tell you whether a given on/off ratio, four weeks on and one off, or any other, prevents or reverses it. That last sentence is the actual gap, and it stays a gap after reading every paper above.

“You need to cycle it” usually bundles together three separate claims that have entirely different evidence behind them.

Tolerance, getting less effect from the same dose over time, is the one with real human measurements, and only for the GH secretagogue family: the GHRP-2 study above measured a falling peak GH response over 5 days of daily injections in 9 men, and the 6-hour GHRH infusion studies measured a blunted response within the same day. Nobody has measured tolerance for BPC-157, TB-500, GHK-Cu, MOTS-c, thymosin alpha-1, selank, semax, epitalon, PT-141, or melanotan-2 at any dosing interval, because no published study has dosed any of them repeatedly for long enough to look.

Dependence, an effect that requires continued dosing and reverses once you stop, is different from tolerance and different again from withdrawal. It has been measured for one class here: GLP-1 receptor agonists. When the STEP 1 trial stopped semaglutide after 68 weeks, participants regained about two-thirds of the weight they had lost within a year off the drug (Wilding et al., Diabetes Obes Metab 2022, PMID 35441470, 327 participants). That is not a withdrawal syndrome, nothing measured got worse than baseline, it is the underlying condition returning once the drug's effect stops. It is also the actual evidence behind why these drugs are prescribed continuously rather than in a cycle: stopping has been measured, and what it does is give the benefit back.

Nothing happening is the honest label for everything else in this catalogue where cycling is discussed. No published study has looked for tolerance, dependence, or a rebound effect from stopping BPC-157, TB-500, GHK-Cu, MOTS-c, thymosin alpha-1, selank, semax, epitalon, PT-141, or melanotan-2, at any interval. That is not the same as a clean bill of health, and it is not the same as evidence that a break is necessary. It means the question has not been asked in a published study, and a specific cycle length for any of them is not an answer to a question that has an answer, it is a guess with no measurement behind it either way.

A handful of compounds discussed for cycling are also approved prescription drugs, and their labels answer the “should I cycle” question in the plainest way possible: by not including a cycle. Semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) are approved for once-weekly dosing for as long as the condition being treated, type 2 diabetes or obesity, is being managed. Neither label prescribes an off period, and the STEP 1 extension above is the measured reason why: stopping does not reset anything favorably, it gives back the benefit.

Tesamorelin (Egrifta) is approved as a daily injection for HIV-associated visceral fat, taken continuously for as long as treatment is indicated. Its label does not include a cycling schedule, despite tesamorelin being, mechanistically, a stabilized GHRH analogue in the exact same receptor family discussed above. Sermorelin, while it was still an approved product under the name Geref, was dosed daily for children with growth hormone deficiency for as long as treatment was indicated, which in practice meant years, not weeks on and weeks off.

Nothing about an FDA or equivalent approval proves a compound is safe to run continuously forever, and nothing about it proves a cycle is unnecessary for molecules that were never brought through that process at all. What it does show is that for the compounds where a regulator has actually reviewed a full development program, chronic continuous dosing was the regimen that got approved, not a cycle, and that is worth more than a forum convention when the two disagree.