The choice between CJC-1295 with DAC and without is usually framed as a strength question. Longer half-life, stronger drug, fewer injections, so with-DAC reads as the upgrade. That framing fails at both ends. The two versions aren’t two doses of one compound, and the human research doesn’t compare them on potency at all. What the research bears on is shape: whether the growth hormone signal arrives as a burst or as a raised floor. The studies that measured shape directly undercut most of what gets repeated about these peptides and sleep.
The DAC question is about shape
DAC is a chemical hook that binds the molecule to albumin in the blood. That is why Teichman and colleagues (J Clin Endocrinol Metab 2006, PMID 16352683) measured a half-life of 5.8 to 8.1 days across two randomised placebo-controlled ascending-dose trials in healthy adults aged 21 to 61. A single subcutaneous injection produced dose-dependent 2- to 10-fold increases in mean plasma GH lasting six days or more, and 1.5- to 3-fold increases in IGF-1 lasting 9 to 11 days. After repeated dosing, mean IGF-1 stayed above baseline for up to 28 days. The authors named 30 and 60 mcg/kg as best tolerated, and the published dosing interval was weekly.
Ionescu and Frohman (JCEM 2006, PMID 17018654) is the more informative paper, and it is routinely misreported. They sampled blood every 20 minutes across a 12-hour overnight window in healthy men (n=12, four at 60 mcg/kg and eight at 90 mcg/kg), before and one week after a single injection, then ran deconvolution analysis on the GH pattern. Basal trough GH rose 7.5-fold. Pulse frequency was unaltered and pulse magnitude was unaltered. The paper’s own title records the finding: pulsatile secretion of growth hormone persists during continuous stimulation by CJC-1295.
That matters because the result is often reported as pulsatility being abolished or replaced. It wasn’t. The accurate description is that the drug adds a raised trough underneath intact pulses. The authors also reported that the IGF-1 increases didn’t correlate with any parameter of GH secretion, so the common inference that the IGF-1 rise tracks the trough is the authors’ interpretation in discussion rather than a measured relationship. The vendor claim about restoring youthful pulsatility is unsupported by the only study that measured pulsatility, which is a narrower statement than contradicted, and the right one.
The no-DAC version, sold as mod-GRF 1-29, is usually described as clearing within minutes. It is worth knowing that the molecule is tetrasubstituted, at D-Ala2, Gln8, Ala15 and Leu27, specifically to resist DPP-4 cleavage and oxidation. Resisting rapid degradation is the entire point of those substitutions, so calling it pharmacokinetically identical to native GHRH 1-29 is wrong on the chemistry. The commonly quoted 30-minute half-life has no identifiable human source, and no published human pharmacokinetic study, pharmacodynamic study or clinical trial appears in the indexed literature under that name. The 100 mcg figure in circulation comes from forum practice. Citing the CJC-1295 studies to justify daily no-DAC dosing invokes a different molecule with a different duration and a different published interval.
What the growth hormone research measured
Sermorelin is the natural GHRH 1-29 sequence with a natural, minutes-long lifespan. Vittone and colleagues (Metabolism 1997, PMID 9005976) gave 2 mg nightly for six weeks to 11 non-obese men aged 64 to 76 with low baseline IGF-1, with overnight sampling every 20 minutes. Mean nocturnal GH release rose (p<0.02), as did GH peak area (p<0.006) and peak amplitude (p<0.05), while pulse frequency stayed flat. IGF-1 didn’t move. Neither did IGFBP-3, GHBP, weight, BMI, waist-to-hip ratio, or DEXA muscle or fat mass. Two of six strength measures improved along with abdominal crunch endurance. The authors concluded that single nightly GHRH dosing is less effective than multiple daily doses.
Tesamorelin is the outlier with real outcome data. Falutz and colleagues (NEJM 2007, PMID 18057338, NCT00123253) randomised 412 HIV-positive adults with abdominal fat accumulation for 26 weeks and measured visceral adipose tissue by CT, which fell 15.2% on drug against a 5.0% increase on placebo, with triglycerides down 50 mg/dL against up 9 mg/dL. That trial and a second, identically designed 26-week phase 3 trial together supported the 2010 FDA approval. Stanley and colleagues (Lancet HIV 2019, PMID 31611038) then ran 61 HIV-positive adults with fatty liver for 12 months and measured hepatic fat fraction by spectroscopy, finding an absolute reduction of 4.1% and a relative reduction of 37%, with 35% against 4% of participants reaching a fat fraction under 5%. Fasting glucose and HbA1c didn’t differ between groups at 12 months.
A pattern runs through the whole class: raised IGF-1 keeps failing to mean anything happened. Sevigny and colleagues (Neurology 2008, PMID 19015485) gave MK-677 to 563 patients with mild-to-moderate Alzheimer’s for 12 months, saw IGF-1 rise 60.1% at six weeks and 72.9% at 12 months, and found no difference on CIBIC-plus, ADAS-Cog, ADCS-ADL or CDR sum of boxes. Bach and colleagues (JAGS 2004, PMID 15066065) raised IGF-1 by 84% against 17% in 161 hip-fracture patients with no significant functional improvement. Vittone raised nocturnal GH with no IGF-1 movement at all. Target engagement isn’t an outcome.
Ipamorelin deserves a paragraph because its reputation outruns its file. The selectivity claim traces to Raun and colleagues (Eur J Endocrinol 1998, PMID 9849822), measured in rat pituitary cells, anaesthetised rats and conscious swine, where it showed an in vitro EC50 of 1.3 nmol/L. The precise finding is relative rather than absolute: ipamorelin didn’t release ACTH or cortisol at levels significantly different from those seen after GHRH stimulation, even at doses more than 200-fold above its GH ED50, while GHRP-6 and GHRP-2 raised both. That is a real finding, measured against an active reference, in pigs. The human file is a 1999 intravenous PK study in 40 subjects and a 2014 phase 2 randomised trial in 114 bowel-resection patients that missed its primary endpoint, at 25.3 against 32.6 hours to first tolerated meal (p=0.15). No published human trial has measured lean mass, fat mass, strength, recovery, tendon repair or sleep on ipamorelin.
The sleep claim depends on delivery shape
The story that GHRH analogues deepen slow-wave sleep rests on a correlation between deep sleep and the nocturnal GH surge. Jessup and colleagues (Eur J Endocrinol 2004, PMID 15538933) ran the experiment that tests it, infusing a GHRH-receptor antagonist into healthy men aged 20 to 33 for 12 hours overnight, confirming 93% suppression of the GH response, then running polysomnography. Slow-wave sleep percentage was unchanged at p=0.607, and no other sleep parameter moved. The authors concluded that endogenous GHRH is unlikely to participate in the genesis of slow-wave sleep. That was a small crossover with a single night per condition, so it is a strong result against the correlation story rather than a closed question.
What Jessup doesn’t address is whether exogenous pulsatile GHRH promotes deep sleep, and two human studies tested exactly that with positive results. Marshall and colleagues (JCEM 1996, PMID 8772566), working in the Born and Fehm lab at Lübeck, gave 200 mcg of GHRH as four episodic boluses and found enhanced slow-wave sleep against placebo, while REM improved at p<0.05. The episodic-versus-continuous contrast reached p<0.01 for stage 4, with the same total dose given as a continuous infusion doing essentially nothing. Antonijevic and colleagues (Sleep Res Online 2000/2001, PMID 11382894), working with 35 depressed patients and 40 controls, found pulsatile GHRH increased NREM and stage 2 sleep in men and significantly decreased it in women (F=6.0 and 7.1, p<0.05).
The conclusion those studies support is narrower than the one usually drawn in either direction. Episodic delivery has weak positive human sleep evidence, with a sex difference nobody has followed up. Continuous stimulation, which is what DAC produces, has no sleep rationale and one direct experiment showing the same total dose does nothing when delivered that way.
The oral compound has the most detailed sleep dataset. Copinschi and colleagues (Neuroendocrinology 1997, PMID 9349662) studied 8 young and 6 older subjects on MK-677 at bedtime, over 7 days in the young cohort and 14 in the older one. At 25 mg in the young group, stage IV duration rose about 50% with REM up more than 20%, while deviations from normal sleep architecture fell from 42% on placebo to 8% on drug (p<0.03). The older cohort showed roughly 50% more REM and shortened REM latency, but had no placebo arm: six subjects received 2 mg then 25 mg in two sequential fixed-order periods against two baseline days, which is a considerably weaker design than the young-cohort comparison. No replication of either result appears in the indexed literature. Meanwhile the one recent trial that measured sleep as an endpoint, tesamorelin 1 mg for 10 weeks in 22 subjects (eNeurologicalSci, NCT02553603), found no significant change in sleep, fatigue, body composition, physical performance or cognition.
Where MK-677 sits and what it costs
Nass and colleagues (Annals of Internal Medicine 2008, PMID 18981485) ran 65 adults aged 60 to 81 on 25 mg oral daily in a two-year modified-crossover design with primary endpoints at 12 months. Fat-free mass rose 1.1 kg against a 0.5 kg loss on placebo (p<0.001), which is the number everyone quotes. The other co-primary endpoint failed outright, with abdominal visceral fat rising in both arms (p=0.68). Body weight rose 2.7 kg against 0.8 kg while total fat rose 1.8 kg against 1.1 kg, and there was no significant change in any isokinetic strength measure or measure of physical function. The authors listed their own limitation plainly: study power, in both duration and participant number, was insufficient to evaluate functional endpoints in healthy elderly persons. That null is underpowered rather than clean.
On the cost side, fasting glucose rose about 5 mg/dL (p=0.015) and the QUICKI insulin-sensitivity index fell 0.013 (p<0.001). Increased appetite occurred in 67% against 36%, which was the one adverse-event difference reaching significance (p=0.02). Edema at 44% against 27% (p=0.3) and muscle pain at 33% against 9% (p=0.1) are frequently quoted without their p-values, and neither reached significance.
Adunsky and colleagues (Arch Gerontol Geriatr 2011, PMID 21067829) gave 25 mg daily to 123 elderly hip-fracture patients for a planned 24 weeks. IGF-1 rose 51.4 ng/mL over placebo and gait speed improved (p=0.011), while stair-climbing power didn’t (p=0.292) and most other functional measures were flat. The trial was terminated early for a congestive heart failure safety signal, and the authors wrote that the compound has an unfavourable safety profile in that population. Secondary sources report 4 cases against 1, a figure the primary abstract doesn’t state.
What the published studies dosed
The parameters below are what researchers administered in published work. They are records of research protocols rather than instructions for anyone.
Tesamorelin was given subcutaneously at 2 mg once daily in both 26-week phase 3 trials and in the 12-month liver-fat trial. The cognition work used 1 mg once daily about 30 minutes before bedtime for 10 to 20 weeks.
CJC-1295 with DAC appears in published human work at 20, 30 and 60 mcg/kg in the multiple-dose study, at 60, 125 and 250 mcg/kg in the single-dose cohorts, and at 60 and 90 mcg/kg in Ionescu, with 30 and 60 described as best tolerated. Dosing was weekly or every other week across 28 to 49 days, and the interval is weekly because the half-life is roughly a week. Figures of 120 and 240 mcg/kg circulate widely and attach to the unpublished ConjuChem phase 2 escalation arms rather than to any published trial, so they don’t belong in a list of studied doses. Daily dosing of this molecule accumulates and has never been studied.
CJC-1295 without DAC has no published human dose.
Ipamorelin’s every human dose in the literature was intravenous, spanning roughly 3 to 100 mcg/kg infused over 15 minutes, plus 0.03 mg/kg twice daily in the failed ileus trial. The subcutaneous route in common use is uncharacterised in humans.
Sermorelin figures, 1 mcg/kg intravenously as a diagnostic bolus and 30 mcg/kg at bedtime in prepubertal children with GH deficiency, come from the Geref and Geref Diagnostic product labeling rather than from a trial report. The elderly-men study used 2 mg nightly for six weeks.
MK-677 was given orally at 25 mg once daily in essentially every substantive trial, with 2, 5 and 10 mg appearing only in sleep and dose-ranging work. Nothing above 25 mg has been studied for a meaningful duration. The sleep study dosed at bedtime.
On timing, the bedtime convention comes from the nocturnal GH surge and from the Marshall episodic-versus-continuous result rather than from a head-to-head trial. No study in any of the five compares morning to evening dosing on any outcome. On duration, the longest controlled exposure in this literature is the Nass two-year crossover, whose second-year data the authors describe as exploratory analyses confirming the one-year results. On monitoring, the measures that actually moved in the trials are the informative ones: fasting glucose and an insulin-sensitivity index for MK-677, body weight and fluid retention, and IGF-1 read as evidence that a compound is doing something rather than as evidence it is working.
Where the evidence is thin
Ipamorelin is thinnest by a wide margin, with two human studies total and no measurement of lean mass, strength, recovery or sleep in either. No-DAC CJC-1295 has nothing. With-DAC has two 2006 pharmacokinetic studies in healthy volunteers, no body-composition, strength or sleep endpoint, and no exposure data past 49 days, because ConjuChem halted the phase 2 program in HIV lipodystrophy on 17 July 2006 after a participant in Argentina died hours after his eleventh weekly injection. The FDA Pharmacy Compounding Advisory Committee briefing document (fda.gov/media/183819) reproduces the detail: 192 subjects enrolled, chest discomfort roughly two hours after the eleventh weekly dose, ECG-confirmed acute myocardial infarction, and death about an hour later. The attending physician’s stated view was asymptomatic coronary disease with plaque rupture, and causality was never established in any peer-reviewed publication. No sponsor has restarted development since.
Sermorelin’s brand, Geref, was withdrawn commercially, with EMD Serono’s discontinuation notification letter dated 11 July 2008 and recorded in the Federal Register determination at 78 FR 14032. The FDA later formally determined it wasn’t withdrawn for safety or effectiveness. Everything sold under that name now is compounded.
For recovery specifically, no human randomised trial exists for any of these five on tendon, ligament, cartilage or muscle-injury repair. A 2026 PRISMA scoping review in the American Journal of Sports Medicine (Tewari et al., PMID 42578445) covering six peptides, including CJC-1295, MK-677 and ipamorelin, found roughly two thirds of identified publications were preclinical animal work, with human studies limited to a handful of investigations most of which lacked adequate controls.
Two structural problems sit under all of it. Every body-composition dataset comes from older adults, obese men, frail hip-fracture patients or HIV-positive adults with lipodystrophy, so extrapolating a 1.1 kg fat-free-mass change in 60-to-81-year-olds to a trained lifter rests on nothing published. And a 2019 analysis of material seized by Danish customs (Drug Testing and Analysis, PMID 30136411) identified black-market ipamorelin and modified GRF 1-29 preparations carrying an extra glycine at the N-terminus, which means no dosing inference survives contact with unverified material.
What to read next
Read Ionescu and Frohman (PMID 17018654) and Jessup (PMID 15538933) first, in that order, because between them they reframe the two claims this category is sold on. Then Marshall (PMID 8772566) for the episodic-versus-continuous contrast, which is the result that actually separates the DAC and no-DAC cases. Then Copinschi (PMID 9349662) and Nass (PMID 18981485) for the MK-677 trade in full, reading Nass’s own limitations section rather than its abstract. Then check whether Copinschi’s polysomnography has ever been replicated, since a second study would change the picture more than anything else in this file. For material, the question worth asking is identity by mass spectrometry rather than purity as a percentage, because the Danish work found the wrong molecule rather than a dirty one.
This article is a review of published research. It is not medical advice, and nothing here is a recommendation to use any compound. Several compounds discussed have no published human data and are sold for laboratory research use only.
