There’s no universal number, and the most useful answer starts by splitting peptides into two groups. Classic secretagogues like sermorelin are cycled — weeks on, then a deliberate break. GLP-1 receptor agonists are not, and treating one like a cycle is the most expensive mistake in this category.
The peptide people wrongly cycle
Semaglutide and tirzepatide are peptides too — GLP-1 receptor agonists — and they are chronic medications, not courses. The trial evidence on stopping is unusually clean.
In STEP 1 (n=1,961 adults with obesity, no diabetes), semaglutide 2.4 mg weekly produced −14.9% mean body weight at week 68 versus −2.4% on placebo. SURMOUNT-1 (n=2,539) put tirzepatide at −15.0%, −19.5%, and −20.9% across the 5, 10, and 15 mg doses versus −3.1% at 72 weeks.
Then the discontinuation data, which is the whole point here. In STEP 4 (Rubino et al., JAMA 2021), patients who stopped semaglutide at week 20 regained substantial weight while those who continued kept losing. SURMOUNT-4 (Aronne et al., JAMA 2024) is starker: after 36 weeks on tirzepatide, the group switched to placebo regained about 14% of body weight over the next year, while the group that stayed on lost a further 5.5%. The loss is held by the drug, not by a finished course of it.
And the stakes aren’t cosmetic. In SELECT (n=17,604 with overweight or obesity and established cardiovascular disease, no diabetes), semaglutide 2.4 mg cut major adverse cardiovascular events by 20% relative (HR 0.80). That benefit was measured on continuous treatment — SELECT didn’t test stopping — so it’s reasonable to expect it, too, depends on staying on the drug. Cycling a GLP-1 off doesn’t reset a receptor; it hands back the result.
Why the “break” people want is really a slower ramp
The usual reason people reach for cycling is nausea. In STEP 1 it was the most common side effect, and it clustered during dose escalation. That’s mechanistic, not mysterious: GLP-1 agonists slow gastric emptying, act on hypothalamic and hindbrain appetite circuits, and improve insulin secretion (tirzepatide adds GIP receptor agonism). Nausea follows directly from delayed gastric emptying, which is exactly why it tracks each dose increase and fades as titration slows.
So the fix is the titration schedule, not an off-week. Standard is 0.25 mg weekly to start, stepping roughly every four weeks — 0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg — and slowing down whenever side effects flare. A US-licensed clinician reviews every case and adjusts that schedule; the compounded semaglutide and tirzepatide we use come from LegitScript-verified 503A US pharmacies under physician oversight, and compounded preparations are not FDA-approved and are not FDA-approved generics or equivalents of the branded products.
The peptides that genuinely are cycled
Sermorelin and NAD+ are the other group — and the more honest one, because these cycle lengths come from clinical practice, not large randomized trials. Read what follows as opinion labeled as opinion.
- Sermorelin (a growth-hormone-releasing analog): commonly 3–6 months on, then reassess. Some people run it continuously, others cycle. The rationale for a break is receptor sensitivity, not a trial endpoint.
- NAD+ injection: a loading phase of roughly 4–8 weeks, then weekly or as-needed maintenance.
We don’t have a named trial for either cycle length, so we won’t dress these up as proven. “Off” here means stop the peptide entirely, not drop the dose — the break is the point. If you cycle off and feel measurably worse, that’s usable data; if nothing changes, the molecule probably wasn’t doing much.
If you stay on, protect lean mass
One caveat for anyone on a GLP-1 long-term. DXA substudies of GLP-1 trials show a meaningful fraction of the weight lost is lean mass, not only fat. The standard countermeasure is resistance training plus protein in the range clinicians commonly target, roughly 1.2–1.6 g/kg/day. What we don’t yet have is solid long-term data on functional outcomes — strength, mobility, fall risk years out. That’s a real gap, not a solved problem, and worth stating plainly.
The takeaways
- Evidence: GLP-1 receptor agonists are chronic, not cycled — stopping reverses the weight (STEP 4, SURMOUNT-4). The cardiovascular benefit (SELECT) was measured only on continuous treatment, so it most likely holds only while you stay on.
- Clinical judgment: sermorelin and NAD+ are cycled on clinical judgment, not trial data — typical ranges are 3–6 months and a 4–8 week load.
- Our opinion: treat GLP-1 nausea with slower titration, not off-weeks; and if you intend to stop, build a maintenance plan first, because a proven one doesn’t exist yet.
The open question is the one every long-term member eventually asks: can a lower maintenance dose hold the weight the way the full dose did? STEP 4 and SURMOUNT-4 tested stopping, not tapering — so the taper question is genuinely unanswered. That’s the trial we’re waiting on. If you want a clinician to map your own on-ramp, start with the quiz.
