PeptideJournal
Comparisons14 min read

MK-677 vs. CJC-1295/Ipamorelin: GH Boosting

You want to raise your growth hormone levels. You have read enough to know that direct GH injections are expensive, tightly regulated, and come with a side-effect profile that gives endocrinologists pause.

You want to raise your growth hormone levels. You have read enough to know that direct GH injections are expensive, tightly regulated, and come with a side-effect profile that gives endocrinologists pause. So you start looking at secretagogues — compounds that tell your own pituitary gland to release more GH rather than injecting it from the outside.

Two options dominate the conversation: MK-677 (ibutamoren), an oral ghrelin mimetic you swallow as a capsule, and the CJC-1295/ipamorelin combination, a pair of injectable peptides that work through the GHRH pathway. Both raise GH and IGF-1. Both have clinical data behind them. But they differ in mechanism, administration, side-effect profile, and the type of GH release pattern they produce.

This article breaks down exactly how they compare — with real numbers from published trials — so you can have an informed discussion with your healthcare provider.

Table of Contents

  1. Quick-Glance Comparison Table
  2. How MK-677 Works: The Ghrelin Route
  3. How CJC-1295/Ipamorelin Works: GHRH Meets GHRP
  4. GH and IGF-1 Elevations: What the Data Actually Shows
  5. Side Effects: Where the Two Paths Diverge
  6. Administration and Convenience
  7. DAC vs. No DAC: A Critical Distinction
  8. Who Might Choose Which (And Why)
  9. Regulatory Status
  10. The Bottom Line
  11. References

Quick-Glance Comparison Table

FeatureMK-677 (Ibutamoren)CJC-1295/Ipamorelin
Drug classNon-peptide ghrelin mimeticGHRH analog + selective GHRP
AdministrationOral (capsule)Subcutaneous injection
Half-life~4–6 hours (effects last 24 h)CJC-1295 no DAC: ~30 min; Ipamorelin: ~2 h
GH release patternSustained elevation with preserved pulsatilityPulsatile bursts (closer to natural rhythm)
IGF-1 increase+50–84% in clinical trials1.5–3x fold increase (CJC-1295 with DAC data)
Appetite stimulationSignificant (ghrelin pathway)Minimal to none
Effect on cortisolNo significant changeNo significant change (ipamorelin-specific advantage)
Effect on blood glucoseRaises fasting glucose ~5 mg/dL; decreases insulin sensitivityNo significant glucose disruption reported
Longest clinical trial2 years (Nass et al., 2008)49 days (Teichman et al., 2006)
FDA approval statusNot approvedNot approved
WADA statusProhibited at all timesProhibited at all times

How MK-677 Works: The Ghrelin Route

MK-677 is not a peptide. It is a small, orally bioavailable molecule — a non-peptide growth hormone secretagogue originally developed by Merck. It works by binding to the ghrelin receptor (GHS-R1a) in the hypothalamus and pituitary gland, mimicking the action of ghrelin, the body's endogenous hunger hormone.

When ghrelin binds to GHS-R1a, it triggers a signaling cascade that tells somatotroph cells in the anterior pituitary to release stored GH. MK-677 does the same thing, but with one notable advantage: its oral bioavailability exceeds 60%, and a single daily dose maintains elevated GH secretion for a full 24 hours.

Here is what matters mechanistically:

  • Pulsatile secretion is preserved. Unlike exogenous GH injections, which create a single spike and suppress natural production, MK-677 amplifies the body's existing GH pulses. In the Nass et al. trial, pulsatile GH secretion was maintained and amplified at 6 and 12 months, with the increase driven by higher secretion per pulse rather than more frequent pulses.
  • IGF-1 rises alongside GH. Because the pituitary is making more of its own GH, the liver responds with increased IGF-1 production. This rise is observable within two weeks of starting treatment.
  • Cortisol stays flat. Despite activating the ghrelin receptor, MK-677 does not elevate cortisol or ACTH — a meaningful distinction from some other secretagogues.
  • Ghrelin receptor activation increases appetite. This is not a minor footnote. In the Nass et al. trial, 67% of MK-677 subjects reported increased appetite versus 36% on placebo. If you are trying to lose body fat, this is a direct headwind.

Structurally, MK-677 belongs to a family of benzolactam-derived secretagogues originally modeled after GHRP-6. Iterative chemical modifications produced a propenamide derivative that engages the ghrelin receptor selectively while resisting rapid metabolic breakdown — which is why it works orally when peptide-based secretagogues do not.

For a deeper look at what happens when MK-677 is used over months and years, see our MK-677 long-term studies review.

How CJC-1295/Ipamorelin Works: GHRH Meets GHRP

The CJC-1295/ipamorelin combination pairs two peptides that stimulate GH release through complementary but distinct receptor pathways.

CJC-1295: A Modified GHRH

CJC-1295 is a synthetic analog of growth hormone-releasing hormone (GHRH), the 44-amino-acid hypothalamic peptide that signals the pituitary to produce and release GH. Native GHRH has a plasma half-life measured in minutes — it gets chewed up by dipeptidyl peptidase IV (DPP-IV) almost immediately. CJC-1295 solves this with four amino acid substitutions at positions 2, 8, 15, and 27 that block enzymatic degradation.

The version commonly paired with ipamorelin is modified GRF (1-29), also called "CJC-1295 without DAC." It retains a short half-life of roughly 30 minutes, which produces a sharp GH pulse that recedes quickly — mimicking the body's natural pulsatile pattern.

Ipamorelin: The Selective GHRP

Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2) that activates the same ghrelin receptor (GHS-R1a) as MK-677. But here is the difference: ipamorelin is the most selective GH secretagogue ever documented.

In swine studies published in the European Journal of Endocrinology, Raun et al. demonstrated that ipamorelin released GH with an ED50 of 2.3 nmol/kg — comparable to GHRP-6 — without any significant increase in ACTH, cortisol, FSH, LH, prolactin, or TSH. This selectivity held even at doses more than 200 times the GH-releasing ED50. By contrast, GHRP-6 and GHRP-2 both elevated ACTH and cortisol at GH-releasing doses.

For a head-to-head look at ipamorelin versus its less selective cousin, see our ipamorelin vs. GHRP-6 comparison.

Why Combine Them?

CJC-1295 and ipamorelin target different receptors. CJC-1295 binds the GHRH receptor, telling somatotroph cells to synthesize and secrete GH. Ipamorelin binds the ghrelin receptor, amplifying that signal. The two pathways converge on the same cells through different intracellular mechanisms, and the result is synergistic — a GH pulse larger than either compound would produce alone.

Think of it this way: CJC-1295 turns up the volume at the GHRH receptor. Ipamorelin simultaneously turns up the volume at the ghrelin receptor. The pituitary hears both signals at once and responds with a bigger GH burst.

For a detailed look at how to combine these peptides in practice, see our guide on how to stack CJC-1295 and ipamorelin. For a comparison of CJC-1295 with another GHRH analog, read CJC-1295 vs. sermorelin.

GH and IGF-1 Elevations: What the Data Actually Shows

This is where people want numbers. Here they are.

MK-677

The strongest MK-677 data comes from the Nass et al. (2008) randomized controlled trial — a two-year study in 65 healthy adults aged 60–81. At 25 mg/day:

  • 24-hour mean GH rose from 0.37 to 1.0 microg/L at 6 months in a representative subject — roughly a 2.7-fold increase
  • IGF-1 increased to levels matching healthy young adults, approximately a 1.5-fold rise from baseline
  • Fat-free mass increased by 1.1 kg over 12 months versus a 0.5 kg decrease with placebo (P < 0.001)
  • GH pulsatility was maintained throughout the 2-year treatment period; levels returned to baseline after discontinuation

In GH-deficient adults given 50 mg/day, the results were sharper: IGF-1 increased 79% (from 84 to 150 microg/L) and 24-hour mean GH rose 82%. In hip fracture patients, IGF-1 climbed 84% versus 17% with placebo.

A separate caloric restriction study showed MK-677 reversed diet-induced nitrogen wasting. Mean IGF-1 rose to 264 ng/mL versus 188 ng/mL on placebo (P < 0.01), and nitrogen balance swung from -1.48 g/day (placebo) to +0.31 g/day (MK-677).

CJC-1295

The landmark Teichman et al. (2006) trial in the Journal of Clinical Endocrinology & Metabolism tested CJC-1295 with DAC in healthy adults over 28- and 49-day periods:

  • A single injection produced 2- to 10-fold increases in mean plasma GH concentrations lasting 6 or more days
  • IGF-1 rose 1.5- to 3-fold and remained above baseline for 9–11 days after a single dose
  • After multiple doses, IGF-1 remained elevated for up to 28 days
  • GH pulse amplitude increased approximately 7.5-fold relative to placebo
  • Estimated half-life: 5.8–8.1 days

These numbers apply to CJC-1295 with DAC. The no-DAC version (modified GRF 1-29) paired with ipamorelin produces shorter, more pulsatile GH bursts. Direct IGF-1 quantification data for the no-DAC/ipamorelin combination in healthy adults is more limited.

Ipamorelin

Ipamorelin's clinical data is thinner. In healthy subjects, it produces a single, time-limited GH pulse peaking around 40 minutes after subcutaneous injection, with a plasma half-life of roughly 2 hours. Its value in the combination is its selectivity and its synergistic effect when paired with a GHRH analog, not its standalone IGF-1 elevation numbers.

The Comparison

MK-677 has the longest and most robust dataset — two years of double-blind, placebo-controlled data in older adults. CJC-1295 has striking single-dose and multi-dose GH/IGF-1 elevation data, but the longest published trial ran only 49 days. The CJC-1295/ipamorelin combination specifically has limited formal clinical trial data for body composition endpoints in healthy adults.

For a broader comparison of secretagogue approaches versus direct GH therapy, see peptide therapy vs. HGH.

Side Effects: Where the Two Paths Diverge

The efficacy profiles of these compounds overlap meaningfully. The side-effect profiles do not.

MK-677 Side Effects

The Nass et al. trial identified three primary concerns:

  1. Appetite stimulation. Two-thirds of subjects reported increased hunger, a direct consequence of ghrelin receptor activation. This effect generally subsided over the first few months but remained a factor for some participants.

  2. Blood glucose and insulin sensitivity. Fasting blood glucose increased an average of 0.3 mmol/L (~5 mg/dL) with MK-677 (P = 0.015), and insulin sensitivity declined. A shorter study by Chapman et al. (1996) found even sharper glucose increases — from 5.4 to 6.8 mmol/L at 4 weeks with 50 mg dosing, pushing into the pre-diabetic range. For anyone with existing metabolic risk factors, this is a significant concern. The FDA has cited "significant safety risks due to the potential for congestive heart failure in certain patients," leading to the early termination of at least one clinical trial.

  3. Transient edema. Mild lower-extremity swelling occurred in some subjects, consistent with the fluid-retention effects of elevated GH/IGF-1.

CJC-1295/Ipamorelin Side Effects

The side-effect profile is generally milder:

  1. Injection site reactions. Redness, swelling, or discomfort at the injection site — standard for any subcutaneous injection.

  2. Transient flushing or headache. Some users report brief warmth or mild headaches shortly after injection.

  3. No significant appetite stimulation. This is the combination's clearest advantage over MK-677. Ipamorelin activates the same ghrelin receptor as MK-677 but at lower systemic exposure and with much greater selectivity. In published swine data, ipamorelin did not stimulate appetite-related pathways at GH-releasing doses.

  4. No significant glucose disruption. CJC-1295 and ipamorelin have not shown the blood glucose increases documented with MK-677. For people concerned about metabolic health, this distinction matters.

  5. CJC-1295 safety note. CJC-1295 with DAC was in Phase II clinical trials for lipodystrophy and GH deficiency, but research was discontinued after the death of a trial subject. The attending physician attributed the death to preexisting asymptomatic coronary artery disease with plaque rupture — unrelated to CJC-1295 treatment — but trials were terminated as a precaution.

Administration and Convenience

This is often the deciding factor for people who are otherwise undecided.

MK-677

One capsule, once a day, by mouth. No needles. No reconstitution. No refrigeration. No timing around meals or sleep with any published protocol requirement beyond consistency. For people who find injections inconvenient, painful, or anxiety-inducing, MK-677 is straightforwardly easier.

CJC-1295/Ipamorelin

Subcutaneous injections, typically administered 1–2 times daily with the no-DAC version. The peptides are supplied as lyophilized powder, requiring reconstitution with bacteriostatic water. They must be refrigerated after reconstitution. Injection is typically done with an insulin syringe into abdominal or thigh subcutaneous fat.

Many users inject before bed to coincide with the body's natural nocturnal GH pulse. Some protocols add a morning injection. Each injection session takes 5–10 minutes including preparation.

For people already comfortable with injections — diabetics, TRT patients, anyone with subcutaneous injection experience — this is a minor inconvenience. For everyone else, it is a genuine barrier to adherence.

DAC vs. No DAC: A Critical Distinction

If you have read about CJC-1295 online, you have encountered the "DAC vs. no DAC" debate. This is not a minor technical detail — it fundamentally changes how the peptide behaves.

CJC-1295 with DAC includes a Drug Affinity Complex that enables covalent binding to circulating albumin. This extends the half-life from minutes to 5.8–8.1 days. The result: sustained, continuous GH and IGF-1 elevation lasting nearly a week from a single injection. This is what was tested in the Teichman et al. clinical trial.

CJC-1295 without DAC (modified GRF 1-29) lacks this modification. Its half-life is roughly 30 minutes. It produces a sharp GH pulse that resolves quickly, more closely matching normal physiology.

The no-DAC version is specifically what gets paired with ipamorelin in most clinical and anti-aging medicine protocols. The logic: both compounds have short half-lives, both produce GH pulses rather than sustained elevation, and the combination aims to amplify natural pulsatile GH patterns rather than override them.

The with-DAC version is typically used alone, dosed weekly. It produces a different GH release pattern — more tonic, less pulsatile. Whether pulsatile or sustained GH release is "better" depends on the therapeutic goal, and the literature has not definitively settled this question.

For more on how CJC-1295 compares to other GHRH analogs, read CJC-1295/ipamorelin combination studies.

Who Might Choose Which (And Why)

Neither compound is FDA-approved for performance, anti-aging, or body composition purposes. Both are prohibited by WADA. What follows is not a recommendation but a summary of the clinical and pharmacological factors that might inform a conversation with a physician.

Factors Favoring MK-677

  • Needle avoidance. Oral dosing eliminates the injection barrier entirely.
  • Stronger clinical evidence base. Two years of randomized, placebo-controlled data in older adults is more than any other GH secretagogue can claim.
  • Convenience. Once-daily dosing with no preparation, reconstitution, or refrigeration.
  • Recovery from caloric deficit. The nitrogen-balance data suggests MK-677 may counteract muscle loss during caloric restriction — a scenario where the appetite-stimulating effect might actually be welcome.
  • Cost. As a small molecule rather than a peptide, MK-677 is generally less expensive.

Factors Favoring CJC-1295/Ipamorelin

  • Metabolic profile. No documented blood glucose increases or insulin sensitivity declines. For anyone with pre-diabetes, metabolic syndrome, family history of type 2 diabetes, or elevated fasting glucose, this is a meaningful advantage.
  • No appetite stimulation. If body fat reduction is a primary goal, the absence of ghrelin-driven hunger makes the CJC-1295/ipamorelin combination more compatible with caloric restriction.
  • Hormonal selectivity. Ipamorelin's documented selectivity — GH release without ACTH, cortisol, prolactin, or other pituitary hormone changes even at 200x the effective dose — is unmatched among GH secretagogues.
  • Pulsatile GH pattern. The no-DAC version paired with ipamorelin produces sharp GH pulses that closely mimic natural physiology, which some clinicians prefer over MK-677's more sustained elevation pattern.
  • Combination flexibility. Two separate peptides mean dosing of each can be adjusted independently.

Factors That Apply Equally

  • Neither is FDA-approved for any indication
  • Both are prohibited in competitive sport under WADA rules
  • Both raise GH and IGF-1 through stimulation of the body's own pituitary, preserving negative feedback loops
  • Both require medical supervision for safe use
  • Long-term safety data beyond two years is unavailable for either

Regulatory Status

Neither MK-677 nor the CJC-1295/ipamorelin combination is FDA-approved for any therapeutic use. Their regulatory positions differ slightly:

MK-677 was developed by Merck and progressed through multiple clinical trials but was never submitted for FDA approval. It remains classified as an investigational compound. The FDA has flagged it for safety concerns, specifically citing "significant safety risks due to the potential for congestive heart failure in certain patients." It is not legal as an ingredient in dietary supplements. It appears on both the DoD Prohibited Dietary Supplement Ingredients List and the WADA Prohibited List.

CJC-1295 reached Phase II clinical trials through ConjuChem Biotechnologies but was discontinued as a precaution after an unrelated death during trials. It is not FDA-approved.

Ipamorelin was developed by Novo Nordisk and reached Phase II trials for postoperative ileus. It has not been approved for any indication.

The broader FDA crackdown on peptide compounding — which placed 17 peptides on the Category 2 Bulk Drug Substance list in September 2023, followed by tighter restrictions in January 2025 — has affected the availability of both CJC-1295 and ipamorelin through compounding pharmacies. MK-677, as a non-peptide small molecule, is affected by different regulatory pathways but remains equally unapproved.

The Bottom Line

MK-677 and CJC-1295/ipamorelin both raise growth hormone and IGF-1 by stimulating your own pituitary gland rather than introducing exogenous GH. They share that fundamental advantage over direct GH injections: they preserve your body's feedback mechanisms rather than bypassing them.

Where they differ is in everything else.

MK-677 is simpler. Swallow a capsule. No needles. Stronger published evidence base. But it comes with a metabolic cost — elevated fasting glucose, reduced insulin sensitivity, and appetite stimulation that two-thirds of users notice — that may be unacceptable depending on your health profile.

CJC-1295/ipamorelin is more complex. Injectable. Requires reconstitution and refrigeration. Less long-term clinical data. But its metabolic profile is cleaner, its hormonal selectivity is superior, and the absence of appetite stimulation makes it more compatible with fat-loss goals.

There is no universally "better" option. The right choice depends on metabolic health, comfort with injections, specific goals, and physician guidance. Both remain investigational compounds that are not approved by the FDA for any therapeutic purpose.

What you should do with this information: bring it to a healthcare provider who understands growth hormone physiology and can evaluate which approach — if either — makes sense for your individual situation.

References

  1. Nass R, Pezzoli SS, Oliveri MC, et al. "Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial." Annals of Internal Medicine. 2008;149(9):601-611.

  2. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Bhaumick B. "Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults." Journal of Clinical Endocrinology & Metabolism. 2006;91(3):799-805.

  3. Raun K, Hansen BS, Johansen NL, et al. "Ipamorelin, the first selective growth hormone secretagogue." European Journal of Endocrinology. 1998;139(5):552-561.

  4. Chapman IM, Bach MA, Van Cauter E, et al. "Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects." Journal of Clinical Endocrinology & Metabolism. 1996;81(12):4249-4257.

  5. Murphy MG, Plunkett LM, Gertz BJ, et al. "MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism." Journal of Clinical Endocrinology & Metabolism. 1998;83(2):320-325.

  6. Bach MA, Rockwood K, Zetterberg C, et al. "The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture." Journal of the American Geriatrics Society. 2004;52(4):516-523.

  7. Sinha DK, Balasubramanian A, Tatem AJ, et al. "Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males." Translational Andrology and Urology. 2020;9(Suppl 2):S149-S159.

  8. Ishida J, Saitoh M, Ebner N, Springer J, Anker SD, von Haehling S. "Growth hormone secretagogues: history, mechanism of action, and clinical development." JCSM Rapid Communications. 2020;3(1):25-37.

  9. Bowers CY, Granda-Ayala R. "GHRP-2, GHRP-6, and hexarelin." Growth Hormone Secretagogues in Clinical Practice. 2005.

  10. FDA Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A. January 2025 revision.