Last Updated January 22, 2024

 January 22, 2024

Curious about MK-677 vs. Sermorelin?

Peptide researchers are increasingly investigating both MK-677 and sermorelin as alternatives to recombinant human growth hormone (rhGH) treatment.

Naturally, there are many questions about the similarities and differences between these two research chemicals.

This guide will compare MK-677 vs. sermorelin, providing a complete overview of both MK-677 and sermorelin, their potential benefits, and how each may be dosed in an experimental setting.

Disclaimer: Peptides.org contains information about products that are intended for laboratory and research use only, unless otherwise explicitly stated. This information, including any referenced scientific or clinical research, is made available for educational purposes only. Likewise, any published information relative to the dosing and administration of reference materials is made available strictly for reference and shall not be construed to encourage the self-administration or any human use of said reference materials. Peptides.org makes every effort to ensure that any information it shares complies with national and international standards for clinical trial information and is committed to the timely disclosure of the design and results of all interventional clinical studies for innovative treatments publicly available or that may be made available. However, research is not considered conclusive. Peptides.org makes no claims that any products referenced can cure, treat or prevent any conditions, including any conditions referenced on its website or in print materials.


What is MK-677?

MK-677 is one of several code names for ibutamoren, an orally active selective agonist of the ghrelin receptor. The compound is known to stimulate the production and secretion of both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) [1].

As mentioned, MK-677 mimics the digestive hormone ghrelin and is chemically indistinguishable from GHRP-6. It binds to growth hormone secretion receptors (GHS-Rs) and has a pronounced effect on GH release without significantly affecting prolactin, thyroxine, luteinizing hormone, or aldosterone. Given its mechanism of action, there is strong research interest in whether MK-677 could be a safer alternative to exogenous GH therapy [2].

MK-677 has yet to pass Phase II clinical trials and its current status is that of a research chemical. The U.S. Food and Drug Administration classifies MK-677 as an Investigational New Drug and its highest known developmental phase is the ongoing Lumos Pharma Phase II trial for somatropin deficiency [3].

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MK-677 vs Sermorelin


Benefits of MK-677

While MK-677 is a research chemical with no formally recognized clinical use, it has been investigated in a number of studies [4, 5, 6, 7, 8, 9, 10, 11].

These studies have yielded promising findings in terms of MK-677’s ability to positively impact subjects’ body composition, sleep, and bone health.

MK-677 and Body Composition

Growth hormone secretagogues like MK-677 are known to positively affect the body composition of research subjects [4, 5].

According to one study involving children with growth hormone deficiency, MK-677 administration can significantly increase GH, IGF-I, and IGFBP-3 levels within just seven days, resulting in positive effects on body composition [6].

In healthy, non-GH deficient test subjects, MK-677 has been shown to reverse diet-induced catabolism when administered at doses ranging from 5-25 mg per day. In another short-term study, researchers observed a reduction in diet-induced catabolism in subjects who took MK-677, noting that the compound was beneficial for maintaining lean muscle mass [7].

MK-677 has also been investigated in obese test subjects, with researchers finding that daily MK-677 administration of 25mg resulted in the subjects gaining 3kg of sustained fat-free mass compared to placebo [8].

MK-677 and Sleep

MK-677 likewise appears to increase the duration of both REM (rapid eye movement) and stage 4 sleep in test subjects.

In an early MK-677 sleep study, test subjects experienced a 20% increase in rapid-eye-movement (REM) sleep and a 50% increase in stage 4 sleep when administered MK-677 at 25mg per day compared with placebo. This finding has led to strong research interest in the beneficial effects of MK-677 with regards to sleep and the compound’s ability to correct age-associated deficiency [9].

MK-677 and Bone Health

MK-677 lastly appears to have a positive effect on the bone health of elderly test subjects, specifically on bone resorption and formation.

According to a nine-week study by Murphy et al., elderly patients administered MK-677 experienced a 29.4% increase in serum osteocalcin compared with those who received placebo, with researchers noting a significant improvement in bone formation [10]. In a phase IIb study by Adunsky et al. found that MK-677 treatment was beneficial for a group of elderly patients recovering from hip fracture [11].


What is Sermorelin?

Sermorelin is a human growth hormone-releasing hormone (GHRH) analog that contains the first 29 amino acids of GHRH, making it the shortest synthetic peptide to have the full biological activity of GHRH. Sermorelin works by stimulating the secretion of human growth hormone from the anterior pituitary [12].

While MK-677 is administered orally, sermorelin is typically administered by subcutaneous injection. It was previously available as an FDA-approved medication under the brand names Geref and Gerel, but its approval was pulled in 2008 for commercial reasons [13].

Sermorelin is currently classified as a research chemical and is commonly available as sermorelin acetate, which is simply the acetate salt form of regular sermorelin.

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Benefits of Sermorelin

While sermorelin is classified as a research chemical, it was FDA-approved (until 2008) to diagnose and treat growth hormone deficiency in children. Researchers are currently studying sermorelin for potential benefits like fat loss, sleep improvement, and anti-aging.

Sermorelin and Fat Loss

Sermorelin is currently being studied for its potential fat loss benefits. In a comprehensive review of growth hormone secretagogues conducted by Sinha et al, the authors cited a number of studies to support their position that sermorelin may be used to manage body composition in men with metabolic syndrome or subclinical hypogonadism (SH). The authors noted that like MK-677, sermorelin is a potent stimulator of both GH and IGF-1, and can thus yield significant increases in lean body mass across a variety of subject populations [14].

Sermorelin and Sleep

There is strong research interest in the effect of sermorelin on sleep. A study on rainbow trout showed that sermorelin could stimulate the production and secretion of HGH and orexin, a neurochemical that helps regulate the sleep cycle. Research has revealed that sermorelin supports proper orexin secretion and function, enabling growth and healing processes to take place during sleep [15].

Sermorelin and Anti-aging

Researchers are also investigating sermorelin as an anti-aging peptide following a swine study showing that sermorelin had a significant impact on the rate of cardiac tissue growth and repair after subacute ischemic cardiomyopathy had been induced [16]. The peptide may also have an effect on skin quality and appearance, as well as on healing that may take place as a result of improved sleep.


MK-677 vs. Sermorelin | Similarities and Differences

Researchers curious about MK-677 vs. sermorelin should know that there are notable similarities and differences between these two research chemicals.

The Similarities Between MK-677 vs. Sermorelin

Here are the main similarities between MK-677 vs. sermorelin.

Regulatory Status

MK-677 and sermorelin are both research chemicals and not FDA-approved treatments. Both are available online to licensed researchers and laboratory professionals.

Treatment for Somatotropin Deficiency

Both MK-677 and sermorelin have at various points been investigated as potential treatments for somatotropin deficiency. MK-677 is currently being investigated in an ongoing Lumos Pharma Phase II trial, while sermorelin was, prior to 2008, an FDA-approved medication used to diagnose and treat children with idiopathic growth hormone deficiency [3, 12].

Favorable Safety Profile Compared with rhGH

Lastly, both MK-677 and sermorelin appear to have a favorable safety profile compared to recombinant GH. Although MK-677 and sermorelin work along different pathways (MK-677 is a ghrelin receptor agonist, while sermorelin is a GHRH analog), they both stimulate the natural production and secretion of HGH. Neither has been linked to the same side effects as recombinant GH, such as increased all-cause mortality in GH deficient children and increased risk of harm in GH deficient adults [4, 17, 18].


The Differences Between MK-677 vs. Sermorelin

Despite a number of similarities between MK-677 vs. sermorelin, there are areas where these research chemicals differ, including their respective routes of administration and regulatory histories.

Route of Administration

A key difference between MK-677 vs. sermorelin is that the former may be administered orally, while the latter is administered via subcutaneous injection. This is thanks to MK-677’s high oral bioavailability of over 60 percent [4, 12].

Half-life

MK-677 has a half-life of 24 hours and may be dosed once daily. By contrast, sermorelin has a much shorter half-life of 11-12 minutes from the subcutaneous injection [4, 12].

Mechanism of Action

MK-677 is an agonist of the ghrelin receptor and works via the pituitary and the hypothalamus, meaning that its action is specific to the GHS-R. By contrast, sermorelin is a GHRH analog that mimics endogenous GHRH activity to stimulate the release of GH [4, 12].

Research and Regulatory History

While sermorelin has had FDA approval as a treatment for children with idiopathic growth hormone deficiency, MK-677 has yet to pass a phase II clinical trial. The majority of studies involving MK-677 have involved small sample sizes, whereas the research on sermorelin has been robust enough to warrant FDA approval [4, 12, 13].


Recommended Research Dosage

Both MK-677 and sermorelin are research chemicals that lack uniform dosing guidelines. We can thus look to the research on both compounds to see how they have been dosed and cycled in past studies and trials.

MK-677 Dosing/Cycles

In the bulk of MK-677 studies, researchers have dosed this research chemical in the range of 12.5-25 mg, including in longer-term studies with durations of 24-52 weeks.

For reference purposes, a sample MK-677 dosing schedule for a wound healing/regeneration protocol would be as follows:

  • MK-677 Dosage: 12.5-25mg of MK-677, ingested orally in liquid or capsule form.
  • Study Duration: Four to eight weeks, depending on the severity of the lesion or injury.
  • MK-677 Cycle: MK-677 is not typically cycled but administered to achieve a given research objective. Subjects should be monitored for insulin resistance for the duration of the MK-677 study.

Sermorelin Dosing/Cycles

Since sermorelin was previously an FDA-approved drug, it has a more clearly defined set of dosage guidelines [12].

Researchers may refer to the following sample sermorelin dosage protocol in wound healing/regeneration contexts:

  • Sermorelin Dosage: 200mcg to 300mcg, delivered via subcutaneous injection once daily at bedtime.
  • Study Duration: 12-24 weeks.
  • Sermorelin Cycle: After each sermorelin course, research subjects should typically be provided with a rest period equivalent to the duration of the study.
  • Notes: Sermorelin vials of 2mg and 5mg are available.

MK-677 vs Sermorelin


Where to Buy Peptides Online? | 2024 Edition

Researchers interested in exploring the benefits of MK-677 or sermorelin may be curious about where to order these compounds online.

At Peptides.org, we have considerable experience dealing with all the major research chemical retailers in the industry.

Below, we’ll present our top two recommended sources of reference materials—one for MK-677 and one for sermorelin.

Chemyo for MK-677

Chemyo is a well-known research chemical vendor with years of experience serving the research community. Here are some of the reasons as to why we rate them highly:

  • Third-Party Tested MK-677: Chemyo submits each batch of MK-677 for third-party mass spectrometry and high-performance liquid chromatography (MS-HPLC) to ensure purity levels of at least 99%.
  • Great Prices: MK-677 50mL (25mg/mL) bottles retail at $80, which represents great value given the product’s research-grade quality.
  • Fast Shipping: All U.S. orders over $100 ship free and typically arrive within 2-3 business days, while the company extends free shipping to international orders over $275.

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Core Peptides for Sermorelin

Core Peptides is a premier vendor of GH secretagogues and other research peptides, standing out in the following ways:

  • Lab-Tested & USA Made: Core Peptides’ sermorelin and other reference materials are all synthesized in certified US laboratories and subsequently undergo third-party lab testing to ensure their suitability for high-level research.
  • Convenient Payments: Core Peptides facilitates a range of convenient payments, including credit cards, Zelle, CashApp, and electronic checks.
  • Great customer service: The vendor boasts an excellent customer service team that is available via email to quickly address any customer concerns.

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Side Effects and Safety

There are some differences between MK-677 and sermorelin in terms of their reported side effects and safety.

A year-long trial involving 65 healthy, elderly subjects found that MK-677 produced the following side effects in some of the patients [19]:

  • Decreased insulin sensitivity
  • Decreased low-density lipoprotein cholesterol
  • Muscle pain (mild, transient)
  • Edema (mild, transient)
  • Increased cortisol levels
  • Increased appetite
  • Increased fasting blood glucose levels (0.3 mmol/L, 5 mg/dL on average)

Due to the limited data available, it is difficult to draw any conclusions about the long-term safety of MK-677.

By contrast, sermorelin has been far more extensively studied and sermorelin side effects are much better understood. The most common reported side effects are [12, 20, 21]:

  • Flushing or redness in the face
  • Swelling, achiness, redness, or discomfort at the injection site
  • Nausea Vomiting
  • Loss of color in the face or paleness
  • Headaches

Some of the rarer side effects associated with sermorelin include [20]:

  • Rashes
  • Itching
  • Difficulty breathing/shortness of breath
  • Hives
  • Tightness in chest
  • Inflammation/swelling

MK-677 vs. Sermorelin | Verdict

In summary, researchers who are curious about MK-677 vs. sermorelin should know that these research chemicals have notable differences in terms of their mechanisms of action and potential effects.

MK-677 is a ghrelin receptor agonist, while sermorelin is a GHRH analog that has been previously approved as a treatment of growth hormone deficiency in children.

Researchers should be further aware that MK-677 has a longer half-life than sermorelin, and a much higher oral bioavailability making once-daily oral administration possible.

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References

  1.  Patchett AA, Nargund RP, Tata JR, Chen MH, Barakat KJ, Johnston DB, Cheng K, Chan WW, Butler B, Hickey G, et al. Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7001-5. doi: 10.1073/pnas.92.15.7001. PMID: 7624358; PMCID: PMC41459.
  2. Bowers CY. Growth hormone-releasing peptide (GHRP). Cell Mol Life Sci. 1998 Dec;54(12):1316-29. doi: 10.1007/s000180050257. PMID: 9893708.
  3. Ibutamoren – Lumos Pharma/Merck – AdisInsight. (2022). Retrieved 6 January 2022, from https://adisinsight.springer.com/drugs/800007434
  4. Sigalos JT, Pastuszak AW. The Safety and Efficacy of Growth Hormone Secretagogues. Sex Med Rev. 2018 Jan;6(1):45-53. doi: 10.1016/j.sxmr.2017.02.004. Epub 2017 Apr 8. PMID: 28400207; PMCID: PMC5632578.
  5. Smith RG. Development of growth hormone secretagogues. Endocr Rev. 2005 May;26(3):346-60. doi: 10.1210/er.2004-0019. Epub 2005 Apr 6. PMID: 15814848.
  6. Codner E, Cassorla F, Tiulpakov AN, Mericq MV, Avila A, Pescovitz OH, Svensson J, Cerchio K, Krupa D, Gertz BJ, Murphy G. Effects of oral administration of ibutamoren mesylate, a nonpeptide growth hormone secretagogue, on the growth hormone-insulin-like growth factor I axis in growth hormone-deficient children. Clin Pharmacol Ther. 2001 Jul;70(1):91-8. doi: 10.1067/mcp.2001.116514. PMID: 11452249.
  7. Murphy MG, Plunkett LM, Gertz BJ, He W, Wittreich J, Polvino WM, Clemmons DR. MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism. J Clin Endocrinol Metab. 1998 Feb;83(2):320-5. doi: 10.1210/jcem.83.2.4551. PMID: 9467534.
  8. Svensson J, Lönn L, Jansson JO, Murphy G, Wyss D, Krupa D, Cerchio K, Polvino W, Gertz B, Boseaus I, Sjöström L, Bengtsson BA. Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure. J Clin Endocrinol Metab. 1998 Feb;83(2):362-9. doi: 10.1210/jcem.83.2.4539. PMID: 9467542.
  9. Copinschi G, Leproult R, Van Onderbergen A, Caufriez A, Cole KY, Schilling LM, Mendel CM, De Lepeleire I, Bolognese JA, Van Cauter E. Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man. Neuroendocrinology. 1997 Oct;66(4):278-86. doi: 10.1159/000127249. PMID: 9349662.
  10. Murphy MG, Bach MA, Plotkin D, Bolognese J, Ng J, Krupa D, Cerchio K, Gertz BJ. Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. The MK-677 Study Group. J Bone Miner Res. 1999 Jul;14(7):1182-8. doi: 10.1359/jbmr.1999.14.7.1182. PMID: 10404019. Neuroendocrinology. 1997 Oct;66(4):278-86. doi: 10.1159/000127249. PMID: 9349662.
  11. Adunsky A, Chandler J, Heyden N, Lutkiewicz J, Scott BB, Berd Y, Liu N, Papanicolaou DA. MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study. Arch Gerontol Geriatr. 2011 Sep-Oct;53(2):183-9. doi: 10.1016/j.archger.2010.10.004. Epub 2010 Nov 9. PMID: 21067829.
  12. Prakash A, Goa KL. Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs. 1999 Aug;12(2):139-57. doi: 10.2165/00063030-199912020-00007. PMID: 18031173.
  13. Determination That GEREF (Sermorelin Acetate) Injection, 0.5 Milligrams Base/Vial and 1.0 Milligrams Base/Vial, and GEREF (Sermorelin Acetate) Injection, 0.05 Milligrams Base/Amp, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness. (2021). Retrieved 3 June 2021, from https://www.federalregister.gov/documents/2013/03/04/2013-04827/determination-that-geref-sermorelin-acetate-injection-05-milligrams-basevial-and-10-milligrams
  14. Sinha DK, Balasubramanian A, Tatem AJ, Rivera-Mirabal J, Yu J, Kovac J, Pastuszak AW, Lipshultz LI. Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Transl Androl Urol. 2020 Mar;9(Suppl 2):S149-S159. doi: 10.21037/tau.2019.11.30. PMID: 32257855; PMCID: PMC7108996.
  15. Shepherd, B. S., Johnson, J. K., Silverstein, J. T., Parhar, I. S., Vijayan, M. M., McGuire, A., & Weber, G. M. (2007). Endocrine and orexigenic actions of growth hormone secretagogues in rainbow trout (Oncorhynchus mykiss). Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 146(3), 390-399.
  16. Bagno, L. L., Kanashiro‐Takeuchi, R. M., Suncion, V. Y., Golpanian, S., Karantalis, V., Wolf, A., … & Valdes, D. (2015). Growth hormone–releasing hormone agonists reduce myocardial infarct scar in swine with subacute ischemic cardiomyopathy. Journal of the American Heart Association, 4(4), e001464.
  17. Carel JC, Ecosse E, Landier F, Meguellati-Hakkas D, Kaguelidou F, Rey G, Coste J. Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study. J Clin Endocrinol Metab. 2012 Feb;97(2):416-25. doi: 10.1210/jc.2011-1995. Epub 2012 Jan 11. PMID: 22238382.
  18. Cummings DE, Merriam GR. Growth hormone therapy in adults. Annu Rev Med. 2003;54:513-33. doi: 10.1146/annurev.med.54.101601.152147. Epub 2001 Dec 3. PMID: 12471175.
  19. Nass, Ralf 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 vol. 149,9 (2008): 601-11. doi:10.7326/0003-4819-149-9-200811040-00003
  20. Drugs.com. (2015). Sermorelin acetate. https://www.drugs.com/cdi/Sermorelin-acetate.html
  21. Mayo Clinic (n.d.). Sermorelin (Injection Route). https://www.mayoclinic.org/drugs-supplements/sermorelin-injection-route/side-effects/drg-20065923?p=1

Scientifically Fact Checked by:

David Warmflash, M.D.

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