Peptide time-to-effect reference

A reader who consults a pharmacokinetics page learns that semaglutide has a ~7-day plasma half-life and that sermorelin clears in fifteen minutes. Neither number answers the question that drives most clinical decisions: when can the effect on the endpoint of interest be detected, when does it plateau, and what happens to it across continued dosing or discontinuation. Plasma residence and clinical response are two different timelines, and conflating them is the source of most expectation mismatches in the practitioner peptide literature — a tesamorelin user expecting visceral-fat results at week three is not running into a slow drug, the user is running into a six-month endpoint timeline that the underlying biology requires regardless of how fast or slow the parent compound clears.

This reference page documents what the published clinical literature actually shows about time-to-effect for each peptide on this site. The structure tracks three timelines per molecule: time to detectable change on the trial-grade endpoint, time to plateau effect (the studied duration past which further dosing produces incremental rather than ongoing improvement), and time to reversal after discontinuation. The page sits alongside the peptide pharmacokinetics matrix and the peptide storage and stability reference as the third meta-reference in the corpus — PK answers "how long does the molecule stay in the body," storage answers "how does the molecule survive between manufacture and use," and time-to-effect answers "how long until the clinical thing happens."

The audience is the user who has read that BPC-157 promotes tendon healing and wants to know whether two weeks is reasonable to feel a difference; who has heard that semaglutide produces 15% weight loss but cannot tell whether that should be detectable at week three or week thirty; who has stopped tesamorelin after a six-month course and wants to know how soon the visceral-fat reduction reverts. Setting realistic expectations is itself part of safe practitioner-grade decision-making: a cycle abandoned at week two because nothing happened was a cycle that never gave the published evidence base a chance to manifest, and a cycle continued indefinitely past the published plateau is a cycle running on hope rather than on data.

1. Why time-to-effect matters

The pharmacokinetic question (when is the drug in the blood) and the clinical-effect question (when does the endpoint move) are linked but not identical, and across the peptide field the gap between the two timelines is often large. A 2-minute-half-life intranasal nootropic produces an 8-hour cognitive signal; a 7-day-half-life weekly injection produces a 16-week weight-loss curve whose steepest segment is between weeks 4 and 20; a 4-week tendon-repair cycle in rats produces structural healing in tissue that has long outlasted the parent compound's plasma presence. These are not coincidences. The downstream biological cascade — gene expression, receptor trafficking, cellular migration, tissue remodeling, metabolic adaptation, behavioral conditioning — is what the clinical endpoint measures, and the cascade runs on biological time rather than on drug-clearance time.

This produces three distinct timeline questions a reader should be able to answer for any peptide they consider:

The cycle-minimum question. What is the shortest published RCT duration that demonstrated the headline effect on the labeled endpoint? A cycle shorter than this duration is running against the evidence base, not toward it. For tesamorelin in HIV-associated visceral fat, the published minimum is 26 weeks (Falutz 2007); for semaglutide on body weight at the 2.4 mg dose, it is 68 weeks of escalation-plus-maintenance (Wilding 2021); for kisspeptin-54 on the centrally mediated arousal endpoint in Comninos's fMRI study, it is essentially a single intravenous infusion (Comninos 2017). The shortest published trial sets the floor.

The plateau question. At what studied duration does the endpoint asymptote — that is, when does additional dosing stop producing meaningful additional improvement? For STEP-1 semaglutide, the asymptote is around week 60–68 of the 68-week trial. For SURMOUNT-1 tirzepatide, it is around week 72 of the 72-week trial — and SURMOUNT-4's lead-in-then-randomized-withdrawal design suggested that further weight loss continues incrementally even at week 88 on the active drug (Aronne 2024). For Nass 2008 MK-677 in healthy older adults, the trial ran two years and the body-composition signal was largely apparent at year one. For Khorram 1997 with the sermorelin analog, body-composition direction was visible at five months but not characterized in cohorts large enough or long enough to define an asymptote.

The discontinuation-reversal question. What does the endpoint do after dosing stops? For semaglutide, the STEP-1 extension (Wilding 2022) showed two-thirds of weight loss regained over 52 weeks off-treatment; for tirzepatide, SURMOUNT-4 placed the regain at 14 percentage points over 52 weeks. For tesamorelin, visceral-fat reduction reverts on discontinuation in extension data — the chronic-therapy framing is structural. For tendon-repair peptides, the tissue repair completed during the cycle is not reversed by stopping; the reversal question simply does not apply in the same shape.

The honest framing is that the answer to all three questions is genuinely different across peptides, and the practitioner pattern of treating "peptides" as a single class with a uniform time-to-effect profile (4 weeks, 6 weeks, 12 weeks — pick a number, run a cycle) is at odds with the underlying clinical data.

2. Per-endpoint timing concepts

Five timing concepts recur across the corpus, each with characteristic durations and each independent of plasma half-life.

Acute pharmacology. Single-dose pharmacological response, typically measurable within minutes to hours. The acute GH pulse after a sermorelin injection peaks at roughly thirty minutes and resolves within two to three hours regardless of whether downstream IGF-1 changes are eventually produced (Khorram 1997, Vittone 1997). The PT-141 erectile response in men with mild-to-moderate ED peaks at approximately thirty minutes post intranasal dose (Diamond 2004). The kisspeptin-induced LH surge in IVF-trigger protocols is detectable within minutes and peaks within ~2 hours (Abbara 2017). The hexarelin GH pulse peaks at ~30 minutes post intravenous dose and resolves by ~240 minutes (Imbimbo 1994). Acute pharmacology is what the pharmacokinetic matrix predicts most directly.

Sub-acute clinical effect. Days to a few weeks. The selank anxiolytic response in the Zozulya 2008 trial showed significant improvement by day three across HAM-A and Zung scales, with the "critical responder" subset showing clinical improvement within one to two days (Zozulya 2008). The DSIP sleep-architecture normalization in middle-aged insomniacs reached normal values by the end of the one-week dosing course in Schneider-Helmert's 1986 study (Schneider-Helmert 1986). The GLP-1 nausea adaptation timeline — the period during which dose-escalation-related GI symptoms transition from limiting to tolerable — typically spans the first 4 to 8 weeks of incretin therapy. The semax cognitive signal in Kaplan 1996's operator-performance study persisted for 20–24 hours after a single intranasal dose (Kaplan 1996), with the multi-day course showing sustained effects across the working week.

Chronic clinical effect. Weeks to months. The semaglutide weight-loss curve in STEP-1 detected change within the first 4 weeks of titration and accelerated through weeks 16–24, with the asymptote near week 60–68 (Wilding 2021). The tesamorelin visceral-fat reduction was measured at the 26-week primary endpoint, with the directional change present earlier but not characterized at intermediate timepoints in the pivotal trial (Falutz 2007). The MK-677 lean-mass gain in Nass 2008 was 1.1 kg at one year and broadly stable in the second year, with the IGF-1 elevation visible at weeks 2–6 well in advance of the body-composition signal (Nass 2008). The anamorelin lean-mass gain in ROMANA 1 and ROMANA 2 was 0.99 kg and 0.65 kg respectively at the 12-week primary endpoint (Temel 2016). These are not slow drugs in the pharmacokinetic sense — semaglutide reaches steady state in 4–5 weeks and tesamorelin reaches steady state within days. The clinical endpoint takes the time the underlying biology takes.

Maximum effect plateau. The studied duration past which additional dosing stops producing meaningful additional benefit on the labeled endpoint. The semaglutide STEP-1 trial demonstrated the asymptote at the 68-week endpoint with a mean -14.9% body weight change; SURMOUNT-4 demonstrated that further loss continues even on continued tirzepatide through week 88 of the maintenance phase, suggesting the asymptote for tirzepatide may be further out than for semaglutide. The MK-677 IGF-1 elevation in Nass 2008 reached near-young-adult levels by 4–6 weeks and was maintained for the full two years without further increase. The CJC-1295-with-DAC IGF-1 elevation in Teichman 2006 plateaus within one to two weekly doses and is sustained at that level on continued dosing (Teichman 2006).

Maintenance versus reversal. What happens on continued dosing past the plateau, and what happens when dosing stops. The semaglutide and tirzepatide curves continue to drift modestly downward on continued dosing past the published asymptote but the rate is incremental, not the steep early-loss curve. On discontinuation, two-thirds of weight loss regains across 52 weeks for semaglutide and 14 percentage points for tirzepatide (Wilding 2022, Aronne 2024). The tesamorelin visceral-fat reduction reverses similarly on discontinuation. The healing-peptide and tissue-repair endpoints behave differently — tissue completed during the cycle is not "lost," but additional repair on a re-injured tissue would require additional dosing. The framework that applies cleanly to metabolic peptides ("chronic therapy with maintenance dose") does not apply to repair-cycle peptides ("finite course with episodic re-dosing on re-injury"), and conflating the two is a common practitioner error.

3. Per-peptide time-to-effect matrix

The table below documents the published clinical timing for each peptide on this site, organized by endpoint. Where multiple endpoints are characterized for a single peptide, multiple rows are listed. Where no published clinical timing data exists for a peptide and a specific endpoint, the cell is marked explicitly — "no published clinical timing data" rather than estimated. The "Citation" column links to in-corpus research entries where available; external sources are linked by DOI.

Peptide	Endpoint	Time to detectable change	Time to plateau	Citation
Semaglutide	Body weight (obesity dose 2.4 mg)	~4 weeks (~3–4% during titration)	60–68 weeks	Wilding 2021 STEP-1
Semaglutide	HbA1c reduction (T2D)	8–12 weeks	24–28 weeks	Marso 2016 SUSTAIN-6
Semaglutide	Cardiovascular event reduction (SELECT)	Multi-year — earliest separation at ~12–18 months	Through trial duration	Lincoff 2023 SELECT
Semaglutide	Weight regain after discontinuation	~4 weeks (steep early phase)	52 weeks (two-thirds regained)	Wilding 2022 STEP-1 ext
Tirzepatide	Body weight (obesity, max dose 15 mg)	~4 weeks (titration phase loss)	72+ weeks; continued loss through 88 weeks in SURMOUNT-4	Jastreboff 2022 SURMOUNT-1, Aronne 2024 SURMOUNT-4
Tirzepatide	Lifestyle-plus-pharmacotherapy cumulative loss	12 weeks (lifestyle lead-in) then sustained	72 weeks post-randomization	Wadden 2023 SURMOUNT-3
Tirzepatide	Weight regain after discontinuation	First 8–16 weeks (steep early phase)	52 weeks (14 percentage-point regain)	Aronne 2024 SURMOUNT-4
Liraglutide	Body weight (obesity dose 3.0 mg)	~4 weeks	56 weeks	Pi-Sunyer 2015 SCALE
Liraglutide	Cardiovascular event reduction (T2D)	Multi-year; primary endpoint at median 3.8 years	Through trial duration	Marso 2016 LEADER
Retatrutide	Body weight (12 mg dose)	~4 weeks; -7.2% at 24 weeks at 1 mg, more rapid at higher doses	48 weeks studied; -24.2% at 48 weeks not yet at asymptote	Jastreboff 2023 retatrutide Phase 2
Cagrilintide	Body weight (combination with semaglutide)	~4 weeks	Phase 3 ongoing; Phase 1b reached -10.8% at 20 weeks	Enebo 2021 Phase 1b
Tesamorelin	Visceral adipose tissue (HIV-associated lipodystrophy)	Not reported at intermediate timepoints; -15.2% at 26-week endpoint	26 weeks; maintained through 52 weeks in extension	Falutz 2007, Falutz 2010 pooled
Tesamorelin	Liver fat (HIV / MASLD)	6 months endpoint reported; intermediate not characterized	6–12 months	Stanley 2014, Stanley 2019
Tesamorelin	IGF-1 elevation	Within ~1–2 weeks	~4 weeks	Falutz 2007
Tesamorelin	Visceral fat after discontinuation	Reverses within weeks; quantified in extension	Full reversion timeline not characterized	Falutz 2010 pooled
Sermorelin	Acute GH pulse	Minutes post-injection; peak ~30 min	Per-dose, resolves within ~2 hours	Khorram 1997, Vittone 1997
Sermorelin	IGF-1 elevation	~2 weeks	~5 months studied	Khorram 1997
Sermorelin	Lean body mass (older men, single-nightly 2 mg)	Not detected at 6 weeks	Six-week study found body-composition null	Vittone 1997
Sermorelin	Lean body mass / skin thickness (Nle27 analog, nightly 10 µg/kg)	~3 months	5 months	Khorram 1997
CJC-1295 (DAC)	IGF-1 elevation	Within days of first dose	~1–2 weeks at weekly dosing	Teichman 2006
Hexarelin	Acute GH pulse	Minutes; peak at ~30 min IV	Per-dose; tachyphylaxis on repeated dosing	Imbimbo 1994, Rahim 1998
GHRP-2	Acute GH pulse	Minutes; peak at ~30–60 min	Per-dose	Bowers et al., JCEM 1991, 72:975–982
Ipamorelin	Acute GH pulse	Minutes; peak at ~30 min	Per-dose; selectivity preserved across cohort	Raun 1998, Gobburu 1999
Ipamorelin	IGF-1 elevation (rodent / mechanistic)	Within ~1–4 weeks at repeated dosing	Dose-dependent; no large human chronic trial	Raun 1998
Ipamorelin	Postoperative ileus resolution	Days, intra-trial timeframe	5-day trial duration	Beck 2014
MK-677	IGF-1 elevation	2–6 weeks	~6–8 weeks; sustained across 2 years	Nass 2008
MK-677	Lean body mass (older adults, 25 mg/d)	~6 months for detectable signal	1 year; modest growth in year 2	Nass 2008
MK-677	Nitrogen-balance / catabolism reversal	Within 7-day dosing window	Trial-defined endpoint at day 7	Murphy 1998
MK-677	Gait speed post-hip-fracture	24 weeks	Trial terminated early on cardiac safety	Adunsky 2011
Anamorelin	Lean body mass (NSCLC cachexia, 100 mg/d)	Detectable by 6–12 weeks	12 weeks (trial duration)	Temel 2016 ROMANA
Anamorelin	Handgrip strength	Not detected	Co-primary endpoint not met	Temel 2016 ROMANA
BPC-157	Tendon-to-bone healing (rat)	Detectable by day 4–7; full effect across days 14–21	21 days in Krivic 2006 protocol	Krivic 2006
BPC-157	Subjective pain reduction (anecdotal)	Practitioner-reported 1–4 weeks	Not characterized — no human RCT	Practitioner consensus / no published human RCT
BPC-157	Gastric-mucosal protection (rat)	Acute (hours) on co-administration	Days for chronic ulcer protocols	Sikiric 2018
TB-500	Dry-eye signs and symptoms (Thymosin β4 ophthalmic)	28-day course; measured at days 28 and 56	28-day course; effect persisting at day 56	Sosne 2015 Cornea, Sosne 2015 CAE
TB-500	Cardiac repair (rodent post-MI)	Days post-injury at start of treatment	Weeks studied in animal models	Bock-Marquette 2004, Smart 2007
TB-500	Subjective soft-tissue repair (anecdotal)	Practitioner-reported 1–4 weeks	Not characterized — no human RCT for the fragment	Practitioner consensus / no published human RCT
GHK-Cu	Skin gene-expression program (topical)	48–96 hours per application	Days; sustained signal on repeated application	Pickart 2018
GHK-Cu	Skin / hair density (topical, practitioner-reported)	Weeks for subjective effect	Not characterized in modern RCT	Practitioner consensus / no human RCT for hair
KPV	Colitis-symptom reduction (rodent)	Days at typical murine-IBD-model dosing	Weeks across model durations	Dalmasso 2008, Kannengiesser 2008, Xiao 2017
KPV	Subjective IBD-symptom reduction (anecdotal)	Practitioner-reported 1–4 weeks	Not characterized — no human RCT	Practitioner consensus / no published human RCT
LL-37	Antimicrobial / inflammatory endpoints	Mechanistic / preclinical only	Not characterized in human trials for the synthetic peptide	No published clinical timing data
Larazotide	Celiac-disease symptom score (0.5 mg TID)	12-week trial duration; significant at primary endpoint	12 weeks studied; Phase 3 failed for futility	Leffler 2015 Phase 2b
Teduglutide	Parenteral-support reduction (short bowel syndrome)	12–20 weeks	24 weeks studied; long-term in STEPS-2	Jeppesen 2012 STEPS
Semax	Acute cognitive / operator performance	Within hours; sustained 20–24 h after single intranasal dose	Per-dose; multi-day course preserves effect	Kaplan 1996
Semax	Ischemic stroke recovery (Russian protocol)	5–10 day course; regression of deficits across acute window	10-day course duration	Gusev 1997
Selank	Anxiety reduction (GAD / neurasthenia, Russian RCT)	Day 1–3 ("critical responders"); day 7–14 broader cohort	14 days (full trial duration)	Zozulya 2008
Selank	Leu-enkephalin biomarker normalization	14-day course in Zozulya trial	14 days; durability post-trial not characterized	Zozulya 2008
Cerebrolysin	Acute ischemic stroke recovery	10–21 day course; effect measured at day 21 and follow-up	21 days studied; long-term in CASTA / CARS-1	Heiss 2012 CASTA, Muresanu 2016 CARS-1
Dihexa	Cognitive endpoints in humans	No published clinical timing data	Fosgonimeton prodrug Phase 3 failed 2025	Hua 2022 fosgonimeton Phase 1, JPET 2025 retraction landscape
DSIP	Sleep architecture normalization (middle-aged)	1 week of nightly dosing	1-week course; effects sustained 1 week post-treatment	Schneider-Helmert 1986, Schneider-Helmert 1987
DSIP	Sleep architecture (elderly)	Delayed compared with middle-aged — full normalization in follow-up week	2 weeks total (treatment + follow-up)	Schneider-Helmert 1986
Thymosin α-1	Chronic hepatitis B response (6-month course)	Detectable by 6 months endpoint	6–12 months in pivotal trials	Andreone 1996
Thymosin α-1	COVID mortality (observational)	Days-weeks in acute setting	Course-dependent	Liu 2020
MOTS-c	Insulin sensitivity / glucose handling (mouse)	Days–weeks at repeated dosing	Weeks at study durations	Lee 2015
MOTS-c	Human clinical endpoint	No human interventional trial published	No human clinical timing data	Du 2018 (observational), D'Souza 2020 (cross-sectional)
Epitalon	Telomerase activity (in vitro)	Days in cell culture	Cell-passage-limited	Khavinson 2003
Epitalon	Human clinical endpoint	No modern RCT published	No characterized timing	Khavinson-program cohorts; not Western-trial-validated
ARA-290 (cibinetide)	SFN symptom score (sarcoidosis)	4 weeks (trial duration)	4–6 weeks studied; persisting in follow-up	Heij 2012 pilot, Dahan 2013
ARA-290	Corneal small-nerve-fiber regeneration	28 days dosing; structural change at end of course	4 weeks; long-term not characterized	Dahan 2013
SS-31 (elamipretide)	Six-minute walk distance (PMM, IV dose-escalation)	5 days	5-day trial duration	Karaa 2018 MMPOWER-2
SS-31	Six-minute walk distance (PMM, chronic subq)	24 weeks — primary endpoint not met	Not differentiated from placebo at 24 weeks	Karaa 2023 MMPOWER-3
SS-31	Six-minute walk distance (Barth syndrome, OLE)	36 weeks open-label extension	36 weeks (significant); 168-week durability	Thompson 2021
SS-31	EZ preservation (dry AMD)	48 weeks (secondary signal)	Trial duration	Ehlers 2024 ReCLAIM-2
PT-141 (bremelanotide)	Acute erectile response (men)	~30 minutes post intranasal	Per-dose, ~6–10 hours	Diamond 2004
PT-141	Sexual desire / HSDD endpoint (premenopausal women)	On-demand 45 min pre-activity	Per-dose; sustained across study period	Kingsberg 2019 RECONNECT
Melanotan II	Tanning (downstream melanocyte response)	Days-to-weeks at loading dose	Weeks; ongoing maintenance	No regulatory trial — gray-market dose-response only
AOD-9604	Weight loss (obesity, 1 mg oral)	~12 weeks in Phase IIa conference data	12 weeks; Phase IIb did not differentiate	Herd 2005 Phase IIa, Stier 2013
5-Amino-1MQ	Human endpoint	No published clinical timing data	No human trials	Neelakantan 2018 (mouse only)
Gonadorelin	LH / FSH pulse (acute)	30–60 min per pulse	Per-dose	Belchetz et al., Science 1978, 202:631–633
Gonadorelin	Testicular function restoration (pulsatile pump)	Weeks–months	Months (spermatogenesis cycle)	Crowley et al. 1985
hCG	Intratesticular testosterone (TRT-adjunct)	Days–weeks per dose	3-week trial in Coviello	Coviello 2005
hCG	Spermatogenesis recovery (post-TRT)	Months	Mean ~6.2 months follow-up in Hsieh series	Coviello 2005 (mechanism)
Kisspeptin	LH surge (IVF trigger)	Minutes; peak ~2 hours	Per-dose, single bolus	Abbara 2017
Kisspeptin	Limbic-circuit activation (sexual/emotional fMRI)	Acute, during single 75-minute infusion	Per-dose, per-stimulus	Comninos 2017
Kisspeptin	Anxiety reduction (generalized)	Not significantly different from placebo	Endpoint not met	Mills 2025

Notes on the matrix. Where multiple endpoints are characterized for a single peptide, the matrix lists them as separate rows; this is structural to the temporal-pharmacology framing — a single molecule can have minutes-scale acute pharmacology, weeks-scale subacute clinical signal, and months-scale chronic clinical endpoint all simultaneously, and reporting them as a single "time-to-effect" estimate would conflate timelines that are biologically distinct. The "time to detectable change" column reports the earliest published timepoint at which a statistically meaningful change versus placebo was reported in the cited trial; this is not necessarily the same as the earliest a user would subjectively "feel" the effect, which is a different question. The "time to plateau" column reports the studied duration at which the trial endpoint reached its asymptote or, where the trial ended before asymptote, the trial duration itself with a note. Where the cell is "no published clinical timing data," the molecule has not been characterized at sufficient depth in the human literature to support a timing claim, and the practitioner-grade framing should be treated as inferential rather than evidence-anchored.

4. Class-level synthesis

The per-peptide rows above cluster into a small number of class-level temporal patterns that are pharmacologically meaningful in their own right.

GLP-1 / GIP / glucagon multi-agonist class

The modern incretin class shares a characteristic non-linear weight-loss curve: detectable change at ~4 weeks during titration (~3–5%), accelerating loss through weeks 4–20, an inflection point in the 20–40 week range as appetite suppression accumulates and energy balance shifts, and an asymptote in the 60–72 week range as energy balance approaches equilibrium at the new lower weight. The slope is non-linear because the underlying biology is non-linear — early weight loss reflects acute appetite suppression and water shifts, mid-trial weight loss reflects sustained caloric deficit, and late-trial plateau reflects the body's energy-expenditure compensation as adipose mass falls. The semaglutide STEP-1 curve, the tirzepatide SURMOUNT-1 curve, the retatrutide Phase 2 curve, and the liraglutide SCALE curve all follow this general shape — what differs across the four molecules is the maximum magnitude of weight loss (largest for retatrutide, smallest for liraglutide) and the steepness of the early phase (steepest for tirzepatide and retatrutide).

The HbA1c trajectory in T2D follows a different shape — most of the reduction (~0.5–1.0%) occurs in the first 8–12 weeks as glucose-dependent insulin secretion and gastric-emptying delay take effect; further reduction across weeks 12–28 is incremental; the asymptote is reached well before the weight-loss asymptote. The dissociation between the two endpoints' time courses is one of the structural facts of the class: HbA1c can plateau while weight loss continues. The mechanistic interpretation is that glycemic improvement reflects acute pharmacological effects on β-cell function and incretin signaling, while weight loss reflects cumulative behavioral and metabolic adaptation to chronic appetite suppression.

The discontinuation curve is also class-characteristic: two-thirds regain of lost weight over 52 weeks for semaglutide (Wilding 2022), 14 percentage points over 52 weeks for tirzepatide (Aronne 2024). The early phase of regain is steepest in the first 8–16 weeks off-treatment; the rate slows but does not zero across the studied window. This is why the GLP-1 discontinuation playbook frames the class as chronic therapy rather than as a weight-loss-then-stop intervention — the underlying mechanism (centrally mediated appetite suppression) reverts when the drug clears, and the metabolic adaptations the drug was protecting against (reduced energy expenditure at lower body weight, increased orexigenic drive) resurface on the same timescale.

GH-axis class (GHRH analogs, ghrelin-mimetic secretagogues, MK-677)

The GH-axis class displays a characteristic biomarker-to-endpoint lag. IGF-1 elevation — the biomarker that confirms drug-receptor engagement — is detectable within 1–2 weeks and reaches near-maximum at typical dosing by 4–6 weeks (Nass 2008, Khorram 1997, Teichman 2006). The downstream biological consequences — lean body mass, body composition, fat distribution — lag the IGF-1 elevation by months. Nass 2008 reported a 1.1 kg lean-mass gain at year one on MK-677; the IGF-1 elevation that drove that gain was visible 10 months earlier. Khorram 1997 reported body-composition change at five months with the sermorelin analog; the IGF-1 elevation was visible at two weeks. The biomarker-to-endpoint lag is the load-bearing temporal fact about this class — users who expect body-composition change at week four are not running into a slow drug, they are running into a five-to-six-month endpoint timeline.

The class-defining unresolved question is whether the lean-mass gain produces a corresponding strength gain. Nass 2008 documented mass gain without strength gain at one and two years. The ROMANA 1 and ROMANA 2 anamorelin trials documented the same dissociation in 12-week cancer-cachexia cohorts (Temel 2016). The Adunsky 2011 trial in post-hip-fracture rehabilitation found gait-speed improvement on MK-677 but most other functional measures did not differentiate, and a cardiac safety signal terminated the trial early (Adunsky 2011). The mass-without-strength pattern is reproducible across three trials, two molecules, and three populations on essentially the same mechanism; whether longer treatment duration would produce strength gains is the question the trial duration of those studies cannot answer. The sarcopenia-and-peptides dossier walks the regulatory and clinical consequences in detail.

The discontinuation pattern is also class-characteristic. The Khorram 1997 trial reported transient hyperlipidemia that resolved by the end of the five-month treatment, suggesting that some endocrine adaptations persist during dosing rather than continuously progressing. The longer-duration MK-677 dosing addressed in the MK-677 long-cycle taper playbook and the broader GH-secretagogue discontinuation playbook addresses what happens on dosing past the studied trial duration — diminishing subjective returns at 6–12 months despite sustained IGF-1, the receptor-desensitization and post-receptor adaptation that GPCR pharmacology predicts (/critic/mk-677-tolerance-myth), and the rebound profile on discontinuation. The honest framing across this class: the biomarker (IGF-1) responds within weeks; the endpoint (body composition, functional measures) responds across months; the maintenance and discontinuation timelines are characterized at trial scale only up to 1–2 years for the longest-duration studies.

Healing peptide class

The published clinical timing data for BPC-157, TB-500 (as the LKKTETQ fragment), KPV (in human IBD), and GHK-Cu (in skin / hair density indications) is essentially nonexistent. What exists is preclinical timing data and practitioner anecdote.

The preclinical data for BPC-157 in rodent tendon-to-bone repair characterizes the timeline cleanly. The Krivic 2006 sharp-transection protocol measured outcomes at days 1, 4, 7, 10, 14, and 21 post-injury, with intraperitoneal BPC-157 starting 30 minutes post-surgery; effect was detectable by day 4–7 across functional, biomechanical, and histological endpoints, and reached full magnitude across days 14–21 (Krivic 2006). The Sikiric program's gastric-mucosal protection studies show acute (hours) effects on co-administration in rat ulcer models (Sikiric 2018). Practitioner-reported subjective pain reduction in human use clusters around 1–4 weeks. The gap between the rodent tendon-repair timeline (3 weeks) and the practitioner-reported subjective timeline (1–4 weeks) is consistent in direction, but the absence of a controlled human trial means there is no anchor for the actual time-to-effect on either subjective or structural endpoints in humans.

The thymosin β4 ophthalmic studies are the closest the healing-peptide class has come to characterized human timing. The Sosne 2015 Cornea trial used 28-day dosing with measurement at day 28 and day 56 — effects on ocular discomfort and corneal fluorescein staining were measurable at the end of the dosing course and persisted at the day-56 follow-up (Sosne 2015 Cornea, Sosne 2015 CAE). The full-length thymosin β4 in these trials is not the "TB-500" fragment that circulates in research-channel use; the trial therefore does not directly characterize the timing of any specific fragment-based protocol.

The KPV literature in murine IBD models documents days-scale effects on inflammation markers and weeks-scale effects on tissue histology in standard mouse colitis paradigms (Dalmasso 2008, Kannengiesser 2008, Xiao 2017). The human translation is absent — no controlled human trial of KPV for IBD has been conducted, and the practitioner timing is therefore inferential.

The GHK-Cu literature documents skin gene-expression program changes across 48–96 hours per topical application in cultured fibroblast and ex-vivo skin systems (Pickart 2018). Hair-density effects in the practitioner literature cluster around weeks of consistent topical use, but no modern controlled human trial of GHK-Cu for hair density has been published — the practitioner timing rests on uncontrolled cohort observation and small open-label series rather than RCT data.

The frame that applies to this class: practitioner-reported timing of 1–4 weeks for subjective symptom improvement is mechanistically consistent with the preclinical tissue-repair timelines (which run days-to-weeks for rodent models), but it is not anchored in human-trial timing data, and the discontinuation question is different in shape from the metabolic-peptide class. Tissue repair completed during a cycle is not "lost" on stopping the peptide; further repair would require further dosing on re-injury. The "chronic therapy" framework does not apply.

Russian-origin cognitive and neurotrophic class

Selank, Semax, and DSIP — the Russian-origin peptide class with the deepest published clinical-trial literature outside the Russian regulatory context — share a characteristic ultra-short time-to-effect signature. Selank's anxiolytic effect was reported as significant by day three in the Zozulya 2008 trial, with a "critical responder" subset (40.5% of participants) showing clinically meaningful improvement within 24 to 48 hours (Zozulya 2008). Semax's operator-performance effect persisted 20–24 hours after a single intranasal dose in the Kaplan 1996 trial (Kaplan 1996); the Gusev 1997 stroke-recovery protocol used 5–10 day courses with regression of neurological deficits measured across the acute window (Gusev 1997). DSIP's sleep-architecture effect normalized within the one-week treatment course in middle-aged insomniacs and required a second post-treatment week in elderly cohorts (Schneider-Helmert 1986, Schneider-Helmert 1987).

The shared temporal pattern — days to a few weeks for clinical endpoint, sustained per-dose effects across hours despite minutes-scale parent-compound plasma half-life — reflects the downstream BDNF, NGF, GABA-A receptor subunit, and enkephalin-system biology that closes the plasma-to-clinical-effect gap. The class-distinctive framing is shorter time-to-effect than the GH-axis or metabolic class. This is one of the reasons the practitioner protocols for these molecules typically run two-week to one-month courses rather than multi-month chronic dosing; the underlying clinical literature characterized short-course protocols, and the chronic-dosing question that applies to the metabolic class is less pressing here.

The Russian-trial body's time-to-effect framing is, generally, shorter than the Western GH-axis or metabolic class. Whether this reflects a real biological-mechanism difference (smaller peptides, faster CNS penetration, more immediate behavioral readouts) or a methodological difference (Russian protocols favoring shorter trials, different statistical conventions, smaller sample sizes producing larger between-arm differences) is unresolved. The Selank Russian evidence response addresses the evidence-quality framing. Reading the time-to-effect numbers as both possibly real and possibly artifact is the appropriate stance.

Mitochondrial and longevity class

SS-31, MOTS-c, and Epitalon — the mitochondrial-targeted peptide class — display widely varied time-to-effect profiles depending on the specific endpoint and trial design. The SS-31 acute six-minute-walk improvement in Karaa 2018's MMPOWER-2 dose-escalation trial was measured at day 5 with five days of intravenous dosing; effects were dose-dependent and reached up to 64.5 metres at the highest dose versus 20.4 metres on placebo (Karaa 2018). The chronic-dosing endpoint in MMPOWER-3 — the same 6MWT endpoint with 24 weeks of daily subcutaneous dosing — did not differentiate from placebo (Karaa 2023). The Barth syndrome open-label extension showed significant 6MWT improvement at 36 weeks (95.9 metres) that did not appear in the preceding 12-week placebo-controlled crossover (Thompson 2021). The dry AMD trial ReCLAIM-2 used 48-week dosing with prespecified primary endpoints that were not met; secondary EZ-preservation signals did separate at the 48-week timepoint (Ehlers 2024).

The SS-31 pattern across these trials is informative: acute pharmacology effects (5 days) can be detected when present, but chronic-clinical endpoints in unselected disease populations frequently do not differentiate at 24-week durations on prespecified primary endpoints, and longer-duration open-label extensions in narrowly defined disease (Barth syndrome) produce the signal that the broader trials missed. The molecule's regulatory approval (Forzinity, September 2025) rests on the Barth-syndrome timeline rather than on a generalizable mitochondrial-indication timeline. The mitochondrial peptides dossier walks the class-pharmacology context.

MOTS-c has no published human interventional trial. The mouse-pharmacology data show days-scale insulin sensitivity changes at repeated dosing and weeks-scale exercise-capacity changes in aged animals (Lee 2015, Reynolds 2021). The human time-to-effect estimate for any indication is therefore inferential from mouse-translation extrapolation alone.

Epitalon's modern clinical-trial evidence base is essentially the Khavinson-program cohorts and the 2003 in-vitro telomere-elongation paper (Khavinson 2003). The cell-culture timeline (days to weeks for telomerase induction, additional passages for telomere lengthening) does not translate to a clinical human-endpoint timeline. The 10-to-20-day Russian-protocol courses that the practitioner literature uses have no controlled-trial efficacy data attached.

Sleep and circadian class

The sleep-class peptide data is essentially the DSIP literature already addressed in the Russian-class section above. The clinical timeline runs 4–7 nights of dosing for sleep-architecture normalization in middle-aged insomniacs, with elderly cohorts requiring an additional week of post-dosing follow-up to reach the same normalization. The mechanism is unresolved four decades after sequencing, and the molecule has not progressed past the Schneider-Helmert era's clinical-trial body (Kovalzon 2006).

Sexual function class

The sexual-function-peptide class displays the cleanest acute-pharmacology timing of any class on the site. PT-141 produces an erectile response within ~30 minutes of intranasal dosing in men with mild-to-moderate ED (Diamond 2004) and is approved as Vyleesi for premenopausal HSDD with on-demand 45-minute-pre-activity dosing (Kingsberg 2019 RECONNECT, Simon 2019). The per-dose window is approximately 6–10 hours; the on-demand framing is structural to the dosing schedule.

Kisspeptin's acute pharmacology is similarly fast — the LH surge in IVF-trigger protocols peaks within 2 hours of bolus administration (Abbara 2017), and the limbic-circuit response in Comninos 2017's fMRI study was measured during a 75-minute intravenous infusion (Comninos 2017). The chronic-dosing question is essentially unstudied; the Mills 2025 anxiety-trial did not reach significance on prespecified endpoints (Mills 2025).

The HPG-axis recovery question (hCG, kisspeptin, gonadorelin for spermatogenesis restoration in men exiting TRT) operates on a different timeline. Intratesticular testosterone responds to hCG within weeks at 500 IU every-other-day in Coviello's trial (Coviello 2005); functional spermatogenesis recovery in post-TRT cohorts averages months and depends on the duration of prior suppression. The TRT discontinuation playbook walks the operational protocol.

5. "I started two weeks ago and feel nothing"

The single most common practitioner question — variants of "I started peptide X two weeks ago and feel nothing, is the product real" — usually reflects an expectation mismatch rather than a product problem. The published clinical trial timing for almost every peptide on this site places the detectable change point further out than the user has waited.

For the GLP-1 class, the published change point at the obesity dose is ~4 weeks of titration, and even at that point the typical loss is 3–5% of body weight — a magnitude that is real on the scale but is below what most users subjectively notice as "the drug is working." For the GH-axis class, the IGF-1 biomarker change is detectable at 2–6 weeks, but the body-composition effect that drives most off-label interest is a months-scale endpoint. For tesamorelin, the visceral-fat reduction is a 26-week primary endpoint — there is no published intermediate timepoint at which the typical magnitude of change is characterized, but two weeks is roughly 8% of the way through the trial duration on which the labeled effect was demonstrated.

Subjective placebo effects can produce early "improvement" that is not pharmacological — the well-documented placebo response in psychometric outcomes, the new-protocol motivation effect in body-composition cohorts, the expectation-driven sleep-quality improvement on a sleep-targeting protocol. The opposite is also true: the absence of subjective effect in the first 1–2 weeks is consistent with the pharmacology and does not indicate product failure. For molecules where the published data anchors the change point at week four or week twelve or week twenty-six, the absence of an effect at week two is the expected baseline.

The cycle-shortening pattern in some biohacker forums — running 3–4 week courses of peptides whose published efficacy data sits at 12-week or 24-week or 68-week durations — produces "no effect" outcomes that would have appeared with adequate duration. The mismatch is structural: the literature's labeled endpoint is at a duration that the practitioner protocol does not reach. Whether the abbreviated protocol works for a different endpoint at a different magnitude is an empirical question, but the comparison against the published literature requires matching durations.

The honest framing: a cycle whose duration is shorter than the shortest published trial duration that demonstrated the labeled effect is running outside the evidence base. The user may still subjectively benefit from a 2-week BPC-157 course on tendon discomfort — practitioner anecdote supports a timing pattern in that range — but the user is operating on a non-RCT-anchored timeline. For the metabolic peptides where the published evidence base is multi-month, the abbreviated-cycle pattern produces outcomes that are not the published outcomes.

6. "I've been on this for six months and want to know if it's still working"

The mirror question: a user past the published plateau wondering whether continued dosing is producing continued benefit. For the metabolic peptides, the answer is that the maintenance effects on the biomarker endpoint typically continue while the further-improvement effects on the headline endpoint typically diminish. Semaglutide and tirzepatide produce additional weight loss across continued dosing past the published asymptote, but at a rate that is small relative to the early-trial steep loss (Aronne 2024 showed 5.5% further loss across weeks 36–88 on continued tirzepatide). MK-677 maintains IGF-1 elevation across two years in Nass 2008 (Nass 2008) and produces modest additional lean-mass gain in year two relative to year one, with the metabolic-adaptation pattern (fasting glucose elevation, insulin sensitivity decline, fluid retention) accumulating across the same period.

The receptor-desensitization and post-receptor-adaptation question is the central one for the GH-secretagogue class. The G-protein-coupled receptor agonism that the class operates on produces β-arrestin-mediated downregulation as a general pharmacological principle, and the practitioner-reported "diminishing returns" at 6–12 months on continuous MK-677 dosing is consistent with that pharmacology (/critic/mk-677-tolerance-myth). The IGF-1 biomarker can stay elevated while the perceived subjective effects attenuate — receptor-level adaptation and post-receptor adaptation operate on different timescales than upstream biomarker sensitivity to the drug presence.

Tachyphylaxis versus frank tolerance is a distinction worth keeping straight. Tachyphylaxis is acute desensitization on rapid repeated dosing (Rahim 1998 for hexarelin); tolerance is gradual right-shift of the dose-response curve across months of chronic dosing; receptor-downregulation is the cellular-biology mechanism that underlies both. The mechanistic distinction matters because the practitioner-protocol response to each is different — tachyphylaxis on a short-half-life secretagogue is mitigated by dosing pattern (intermittent rather than continuous); chronic tolerance on a long-acting secretagogue requires either dose-escalation (which the higher-dose-faster-results myth response addresses) or course interruption. The honest framing across the class: diminishing returns past 6–12 months are predicted by GPCR pharmacology and observed in the longest available controlled-exposure datasets; the framing that "tolerance doesn't develop" is inconsistent with both.

The diminishing-returns-versus-frank-tolerance question is also relevant for the GLP-1 class but operates on a different mechanism — appetite suppression as cumulative behavior rather than as receptor-pharmacology trajectory. The continued weight loss past the studied 68-week asymptote on semaglutide is small in magnitude, and the practitioner pattern of "dose-escalating past the labeled max to break a plateau" is not supported by published data and is associated with elevated adverse-event rates rather than further endpoint movement.

7. "When can I stop and expect maintenance"

The discontinuation question is where the time-to-effect framework crosses into the reversal-and-rebound territory that the playbook dossiers address in operational detail. The structural answer differs by class.

Metabolic peptides (GLP-1 / GIP / glucagon, tesamorelin). Most effects partially revert on discontinuation. Semaglutide's STEP-1 extension showed two-thirds of weight regained over 52 weeks (Wilding 2022); tirzepatide's SURMOUNT-4 showed 14 percentage points of regain at 52 weeks (Aronne 2024); tesamorelin's visceral-fat reduction reverses on discontinuation in extension data (Falutz 2010). The class is chronic-therapy-framed; "maintenance" in the sense of stable endpoint without continued dosing is not supported by the published trial body. The GLP-1 discontinuation playbook walks the operational tapering and re-initiation considerations.

GH-axis peptides. The discontinuation pattern is less well characterized — the longest controlled-exposure trial is Nass 2008 at two years, and the explicit discontinuation-cohort follow-up is limited. Practitioner experience clusters around partial reversion of body-composition gains over months on stopping MK-677 and other secretagogues; the IGF-1 biomarker reverts to baseline within weeks. The MK-677 long-cycle taper playbook and the broader GH-secretagogue discontinuation playbook address the operational protocols for the class.

HPG-axis peptides (gonadorelin, hCG, kisspeptin in TRT-adjunct or post-TRT contexts). Testicular-function changes on these molecules are partially reversible — intratesticular testosterone falls within weeks of stopping hCG (Coviello 2005) and spermatogenesis recovery in long-suppressed cohorts averages months on transition off TRT to hCG-plus-clomiphene protocols (Habous 2018). The TRT discontinuation playbook walks the multi-month timeline.

Healing peptides (BPC-157, TB-500, KPV, GHK-Cu). The reversal framework differs in shape. Tissue repair completed during the cycle is not "lost" on discontinuation — a tendon that has remodeled across a four-week course of BPC-157 does not unremodel when the peptide clears. What the discontinuation does is end the active repair stimulus, so any additional repair on a re-injured tissue would require additional dosing. The class-appropriate framing is finite-course-with-episodic-redosing-on-re-injury rather than chronic-therapy-with-maintenance-dose. Practitioner protocols that run continuous BPC-157 dosing for months on end are running outside both the rodent-trial timeline (which characterizes effects across 3-week protocols) and the practitioner-reported timing (which clusters around 1–4 week subjective improvement windows).

Cognitive and neurotrophic peptides (Selank, Semax, DSIP). The course-based framing applies. Published trials run 1–3 week courses; effects appear during the course and persist for follow-up windows that vary by indication. Whether the effect persists past the follow-up window in the studied populations is not characterized for most molecules in this class. The chronic-dosing framing that applies to the metabolic class does not apply; episodic course-based dosing on the published protocols is the closest practitioner translation to the trial-grade evidence.

Mitochondrial peptides (SS-31, MOTS-c, Epitalon). The discontinuation question is least characterized for this class. The SS-31 Barth-syndrome OLE durability data extends to 168 weeks (Thompson 2021 plus subsequent extension), but no explicit discontinuation-cohort follow-up is published; the regulatory framing of Forzinity is chronic therapy for the labeled indication. The mitochondrial-tissue accumulation chemistry that defines SS-31's pharmacology suggests that on-cellular SS-31 may persist substantially longer than plasma half-life would predict, but the discontinuation timeline for that on-cellular pool has not been characterized in human trials.

8. How to read this page

The pharmacological numbers above are not in themselves the point. The point is that the cycle-length conventions in the practitioner peptide field — 4 weeks, 6 weeks, 12 weeks — are often chosen for reasons that do not match the underlying clinical evidence base. A 12-week cycle of tesamorelin is half the duration of the published primary-endpoint window; a 4-week cycle of semaglutide is the titration phase, not the maintenance phase; a 2-week cycle of MK-677 is enough to register IGF-1 elevation but not enough to register the body-composition endpoint that most off-label users are targeting. Matching the cycle length to the endpoint timeline is the diagnostic discipline this page is built to support.

The matrix updates as the literature grows. The current version is dated 2026-05-18. Where the per-peptide-per-endpoint rows note "no published clinical timing data," the matrix reports the absence as information rather than treating it as missing data — the gap between practitioner-reported timing and trial-anchored timing is one of the load-bearing knowledge gaps in the research-channel peptide space, and the editorial discipline this site applies is to report it that way.

Sources cited

In-corpus research entries cross-linked from the per-peptide matrix and the class-synthesis sections include the full set of trials anchoring the time-to-effect claims; they appear inline and are not duplicated here. External primary citations that anchor timing claims not yet represented as in-corpus research MDX entries:

• Belchetz et al., Science 1978, 202:631–633 — pulsatile vs continuous GnRH receptor pharmacology and the LH/FSH-pulse timeline
• Bowers et al., J Clin Endocrinol Metab 1991, 72:975–982 — GHRP-2 acute GH pulse characterization
• Crowley et al., Recent Prog Horm Res 1985, 41:473–531 — pulsatile gonadorelin pump for testicular-function restoration timeline
• Enebo et al., Lancet 2021, 397:1736–1748 — cagrilintide + semaglutide Phase 1b weight-loss trajectory at 20 weeks

In-corpus discontinuation and class-synthesis dossiers:

• GLP-1 discontinuation playbook
• TRT discontinuation playbook
• GH-secretagogue discontinuation playbook
• MK-677 long-cycle taper playbook
• Sarcopenia and peptides
• GH-axis dossier
• GLP-1 receptor pharmacology dossier
• Mitochondrial peptides
• Healing and angiogenesis
• Peptide pharmacokinetics matrix
• Peptide storage and stability reference
• Peptide receptor pharmacology atlas

In-corpus critic responses cross-linked from this reference:

• MK-677 tolerance myth
• Higher-dose-faster-results myth
• Selank Russian evidence