Titus Thorne

Last Updated May 14, 2022

Titus Thorne

 May 14, 2022

Sermorelin vs. ipamorelin.

Curious which of these research peptides is the right one to start researching? This guide should help.

Both sermorelin and ipamorelin work to increase the amount of human growth hormone (HGH) produced and secreted by the pituitary gland.

But while these two peptides can have similar effects, they work in slightly different ways.

In this post, we will present a detailed rundown of both sermorelin and ipamorelin, including how they work, what benefits they offer, and what side effects they may cause when administered to test subjects. 

We will also share our suggestion for the best online vendor currently supplying these peptides to researchers.

Let’s get to it!

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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. 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 are Research Peptides?

Research peptides are short chains of amino acids that are linked by peptide bonds. They range from between two and fifty amino acids in length and fall under many different categories. Some peptides are isolated from natural sources and some are made artificially.

Longer chains of amino acids double over on themselves creating 3D shapes and are classified as proteins. By contrast, peptides are shorter chains that are typically two-dimensional. The US Food and Drug Administration (FDA) classifies chains of 40 amino acids or fewer as “peptides.”

Because of their small, flat structure, peptides are able to bind with a number of chemical receptors throughout the body that larger molecules and drugs cannot access.

The FDA has currently approved over 490 peptide products for a variety of uses. Some of these include treatments and prevention for:

  • Genetic disorders
  • Cancer
  • Infectious disease
  • Cardiovascular issues
  • Eye disorders
  • Immune system weakness
  • Bone disorders and osteoporosis
  • Respiratory disorders
  • Neurodegenerative disorders
  • Eye disorders

Both sermorelin and ipamorelin are peptides and we will explore the differences between them below.


What Is Sermorelin?

Sermorelin acetate, commonly known as sermorelin, is a peptide analogue of human growth hormone-releasing hormone (GHRH). Whereas GHRH is a 44-amino acid peptide, sermorelin contains just the first 29 amino acids of GHRH yet has the same biological activity [1]. In other words, sermorelin is a fully functioning “fragment” of GHRH, making it the shortest peptide to have this ability.

Sermorelin was initially approved by the FDA in 1997 and sold under the trade name “Geref” [2]. It was indicated for the treatment of Growth Hormone Deficiency (GHD) in both children and adults and was also used as a diagnostic agent for assessing whether a patient’s pituitary gland was functioning properly.

Sermorelin’s FDA approval was withdrawn in 2008 for reasons other than safety and efficacy [3].

Mechanism of action

Sermorelin works by mimicking the body’s endogenous human growth hormone-releasing hormone (GHRH). GHRH is a 44-amino acid brain-gut peptide that binds to the growth hormone-releasing hormone receptor (GHRH-R) and stimulates the pituitary gland to produce and release more HGH [4]. While sermorelin contains just the first 29 amino acids of the GHRH protein, its mechanism of action is identical.


Benefits of Sermorelin

Sermorelin’s FDA approval was discontinued in 2008 and it thereby lost its status as being approved for any medical use [3]. However, before being discontinued, sermorelin did have a number of medically recognized benefits. 

Diagnosis and treatment of idiopathic growth hormone deficiency 

Between 1997 and 2008, sermorelin was an FDA-approved drug used to diagnose and treat children with idiopathic growth hormone deficiency [1].

Treatment of hypogonadal symptoms in males

In 2020, Deepankar et al. conducted a review of the role of growth hormone secretagogues (GHS) in the modern management of body composition in hypogonadal males and noted that sermorelin was one of several GHS that can “significantly improve body composition while ameliorating specific hypogonadal symptoms including fat gain and muscular atrophy” [5]. Sermorelin’s proposed clinical use in hypogonadal males and men with SH is “lean mass gain” [5]. 

Potential anti-aging benefits

Sermorelin’s potential anti-aging benefits were first identified by a 1992 study conducted by Corpas et al. that evaluated sermorelin’s effects on GH and IGF-1 levels in 9 young men (22 to 33 years old) and 10 elderly men (60 to 78 years old). The study found that “short term subcutaneous administration of GHRH to healthy old men reverses age-related decreases in GH and IGF-I” [6]. 

A 1997 single-blind randomized placebo-controlled trial by Khorram et al. found that elderly men and women who received nightly subcutaneous injections of sermorelin for 16 weeks experienced a “significant increase in skin thickness” [7]. In men, “lean body mass was significantly increased by 1.26 kg” along with notable “improvements in wellbeing and libido” [5].  

Animal studies have indicated that GHRH agonists may reduce myocardial infarct scarring in swine [8]. However, sermorelin has not been tested for this purpose in human or animal clinical trials. 

In the next section, we’ll discuss what ipamorelin is and the kind of benefits it offers when administered to test subjects.

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What Is Ipamorelin?

Ipamorelin is a pentapeptide (a chain of five amino acids) that was developed by Novo Nordisk, a Danish pharmaceutical company. As a synthetically produced peptide, ipamorelin is chemically similar to GHRP-1, the growth hormone-releasing peptide that’s naturally produced in the body. The main difference between ipamorelin and GHRP-1 is that ipamorelin lacks the central dipeptide Ala-Trp [9].

Unlike sermorelin, ipamorelin has yet to be approved by the FDA for any use and remains a research peptide with a paucity of data regarding its clinical effects. 

Mechanism of Action

How exactly does ipamorelin work?

Ipamorelin is a growth hormone (GH) secretagogue that mimics ghrelin and selectively binds the same GHSR-1a receptor as endogenous ghrelin [10]. This stimulates the pituitary gland to release GH, which in turn influences a range of anabolic processes such as energy usage, fat processing, and appetite suppression [11]. 

What makes ipamorelin unique is that it’s the first GHRP-receptor agonist that stimulates GH release to an extent comparable with endogenous GHRH [9].

Ipamorelin’s secondary action is to reduce the amount of somatostatin — a hormone that inhibits the production and release of HGH. By lowering somatostatin levels, ipamorelin stimulates the pituitary gland to produce more GH  [9].


Ipamorelin


Benefits of Ipamorelin

As ipamorelin lacks FDA approval, it currently offers no approved medical uses. There is a notable lack of data regarding ipamorelin’s clinical effects in humans. However, various studies have observed the following benefits: 

Stimulate body weight gain and GH release in animals

A 1998 paper by K Raun et al. found that ipamorelin could stimulate the release of GH from primary rat pituitary cells and swine [9], and concluded that the peptide could be a “very interesting candidate for future clinical development.” 

A 2002 study published in the European Journal of Anatomy found that ipamorelin treatment could stimulate body weight gain and GH release in young female rats [12]. 

Potential benefits for patients undergoing open laparotomy

In 2014, ipamorelin was briefly investigated in phase II clinical trials for the treatment of postoperative ileus [13]. These trials were discontinued because the “clinical endpoints did not reach statistical significance when comparing ipamorelin to placebo” [5]. However, data from this study indicated that ipamorelin treatment may shorten the recovery times of patients undergoing open laparotomy [14]. 

Potential treatment for hypogonadal males

Ipamorelin was included in the aforementioned review by Deepankar et al. of growth hormone secretagogues (GHS) in the modern management of body composition in hypogonadal males. This review noted that ipamorelin was one of a number of GHS that can “significantly improve body composition while ameliorating specific hypogonadal symptoms including fat gain and muscular atrophy” [5]. Ipamorelin’s proposed clinical use in hypogonadal males and men with SH is “total weight gain” [5]. 


Sermorelin Acetate

 


Differences Between Sermorelin and Ipamorelin?

What are some of the differences between these research peptides?

The primary difference, as detailed above, is that sermorelin and ipamorelin bind to different receptors;

  • Sermorelin is an analogue of growth hormone-releasing hormone (GHRH) and binds to growth hormone-releasing hormone receptors (GHRH-R). 
  • Ipamorelin is a growth hormone (GH) secretagogue that binds to the growth hormone-releasing peptide receptors, GHRP-receptors.

The second difference is that ipamorelin reduces somatostatin, a hormone that inhibits GH. Sermorelin does not have this function.

A third key difference between these two peptides is that sermorelin has passed human clinical trials and received FDA approval — but this was subsequently withdrawn in 2008 [3]. 

To date, ipamorelin has yet to pass clinical trials or receive FDA approval. The only evidence that ipamorelin can stimulate growth hormone (GH) release comes from animal studies [12].  


Ipamorelin


How Are Sermorelin and Ipamorelin Dosed?

Researchers interested in testing with sermorelin and/or ipamorelin should know that these compounds can be dosed in a multitude of ways depending on the purpose of the trial and the age, sex, and weight of the test subject. 

Sermorelin Dosage

During the period where sermorelin was an FDA-approved treatment for idiopathic growth hormone deficiency in children, the indicated dose for long-term treatment was one intravenous injection of 1 mcg per kilogram of body weight per day [1]. 

A study by Gelander et al. evaluated the short-term effects of 1 mg sermorelin per day in children with pulsatile GH secretion [15].

There is limited research on sermorelin’s use in clinical settings, but here is an overview of the dosages used in various clinical trials: 

  • Corpas et al. administered twice daily injections of either 0.5 mg or 1 mg doses of sermorelin for 14 days [6]. 
  • Khorram et al. administered 16 weeks of 10 µg/kg of sermorelin [7].
  • Sigalos et al. administered thrice daily 100 µg doses of a combined GHS therapy ((GHRP)-2, GHRP-6, and sermorelin) for 134 days [16].
  • Vittone et al. administered 2 mg of subcutaneous sermorelin nightly for 6 weeks [17]. 

The most common time for the administration of sermorelin is late at night, at least two hours after eating, or early in the morning, before the first meal of the day. 

Despite strong research interest in the application of sermorelin to improve athletic performance and body composition, there are no published figures to indicate the dosage at which this peptide may be administered to this end. The lack of data in this area indicates that further experimentation is warranted with both sermorelin and a sermorelin-ipamorelin blend.

Ipamorelin Dosage

Since ipamorelin has not been officially approved for human use, it has no “recommended” dosing or cycling structure. However, drawing on data from a 2014 clinical trial, we can see that researchers dosed this peptide as follows [13]:

  • 0.03 mg per kilogram of body weight per day
  • Twice-daily intravenous infusions 

As with sermorelin, there is similarly strong research interest in the application of ipamorelin to improve body composition and performance in healthy individuals. The paucity of data in this area suggests that further research into ipamorelin may be warranted, possibly in conjunction with GHRH analogues like sermorelin, as in a sermorelin-ipamorelin blend.

Directions for handling sermorelin and ipamorelin

When handling either of these peptides, researchers may consider the following directions:

  • To reconstitute sermorelin or ipamorelin, inject the diluent into the vial of sermorelin against the wall of the glass vial. Then swirl the vial until the powder has been completely dissolved. If any particles have not been dissolved or if the mixture is cloudy, do not administer.
  • Any unused mixture should be refrigerated immediately and kept away from light and moisture [18].
  • The best time to administer both ipamorelin and sermorelin is during the late evening before bedtime. That’s because levels of endogenous GH peak at these times. 
  • For both of these peptides, subjects should stay well-hydrated by drinking plenty of water. That’s because the body uses more water than usual while it’s repairing itself.

How to Order Research Peptides Online?

Researchers should have no issues ordering research peptides online. The hardest task facing researchers is finding a reputable peptide vendor that makes good on its promises. 

Peptide researchers should look for vendors that offer: 

  • High-quality products: Insist on a vendor that can prove the quality of their products through independent, third-party analysis. 
  • Customer reviews: A good company will usually leave a footprint on the internet. Look for companies where independent reviewers have given them a high rating.
  • Customer service: Legitimate vendors should be easy to contact. Researchers should try to contact the company before making a purchase.
  • Fair price: Sermorelin and ipamorelin costs should not be super high, or super low. Look for vendors that sell these peptides for reasonable prices. 
  • Refund policy: Look for vendors that offer a money-back guarantee or free reshipments in the event that a shipment is lost or delayed. 

Peptide research isn’t cheap, so researchers should prioritize vendors that offer good quality products.

To assist researchers, our team made a series of test purchases from various vendors and rated them according to cost, shipping times, and customer service. Our favorite vendor by far is Peptide Sciences

We like them because:

  • They provide certificates of analysis for all their products, backing up Research Peptides’ promise that all of their products attain 99% purity.
  • Research Peptides is a US-based company that ships all over the world. Researchers in the US should receive their order within a couple of days, while those based internationally can expect a 7- to 10-day delivery window. 
  • Payment is secure and convenient. They’ll take all major credit cards and they’ll even accept cryptocurrencies like Bitcoin and Ethereum.
  • They have great customer service. Researchers can email Peptide Sciences and get a response from a real person.
  • Refund policy. Research Peptides offers a full 30-day money-back guarantee. 

Overall, we highly recommend Peptide Sciences to any researcher looking to work with sermorelin or ipamorelin.


Side Effects and Safety Concerns?

Before conducting research with either sermorelin or ipamorelin, researchers should understand the possible side effects of administering these peptides to test subjects.

Sermorelin side effects

Although sermorelin’s FDA approval was withdrawn in 2008, this was for reasons other than safety and efficacy [3]. A review of sermorelin’s use in the diagnosis and treatment of children with GHD concluded that “once daily subcutaneous doses of sermorelin are well tolerated” [1]. 

The most commonly reported adverse events were: 

  • Transient facial flushing
  • Pain at the injection site

Citing Sigalos et al.’s study into the use of sermorelin to treat hypogonadal men [16], Deepankar et al. noted that “although rare adverse events such as nausea, facial flushing, and redness at the injection site were noted, sermorelin appears to have a very favorable safety profile” [5].

According to Drugs.com, the most common sermorelin side effects are [18]:

  • Swelling or redness at the injection site
  • Vomiting
  • Headaches
  • Nausea
  • Facial flushing

Research subjects should seek medical attention immediately if they experience any severe allergic reactions such as itching, swelling, rashes, difficulty breathing, or hives. 

Ipamorelin side effects

Based on data from ipamorelin’s discontinued clinical trials, researchers concluded that this peptide was “well-tolerated” at doses of “0.03-mg/kg twice daily for up to 7 days” [8]. 

Citing the available literature, Deepankar et al. noted that adverse effects associated with (ipamorelin) treatment are rare and “similar to those reported with sermorelin” [5].

In the absence of data from any other human clinical trials, little else is known about ipamorelin’s side effects and safety profile. 


Sermorelin Acetate


Sermorelin Vs. Ipamorelin | Verdict

Sermorelin and ipamorelin are similar in that they both appear to stimulate the body to produce more growth hormone.

But they do that by binding to different chemical receptors. That means they can have slightly different effects.

Which is better? 

Sermorelin has the advantage of having passed human clinical trials. It received FDA approval in 1997 and was considered to be safer than somatropin for treating children with idiopathic growth hormone deficiency. 

Compared with ipamorelin, there is more data about sermorelin’s effect on long-term health and this could make it appealing to safety-conscious researchers. It must be stressed that the decision to remove sermorelin’s FDA approval in 2008 was not due to reasons of safety or efficacy.  

Ipamorelin, on the other hand, has never received FDA approval, and its ability to stimulate growth hormone (GH) release has been demonstrated only in animal studies. This means that less is known about its potential impact on human health and this could be a factor for risk-averse researchers. 

In summary, both sermorelin and ipamorelin show clear potential for the treatment of hypogonadism in men and the lack of available data opens opportunities for future investigation. 

To make the best decision about which peptide is the best candidate for further research, researchers should adopt a cautious approach and consider long-term follow-up for research subjects.

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References

  1. 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.
  2. US Food and Drug Administration, (n.d.). Drugs at FDA: FDA-Approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020443
  3. 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 
  4. Xu, Z. (2016). Growth Hormone-Releasing Hormone. In Handbook of Hormones (pp. 144-e18B). Academic Press.
  5. Sinha, Deepankar K 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 vol. 9,Suppl 2 (2020): S149-S159. doi:10.21037/tau.2019.11.30
  6. Corpas E, Harman SM, Piñeyro MA, Roberson R, Blackman MR. Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. J Clin Endocrinol Metab. 1992 Aug;75(2):530-5. doi: 10.1210/jcem.75.2.1379256. PMID: 1379256.
  7. Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab. 1997 May;82(5):1472-9. doi: 10.1210/jcem.82.5.3943. PMID: 9141536.
  8. 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.
  9. Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998 Nov;139(5):552-61. doi: 10.1530/eje.0.1390552. PMID: 9849822.
  10. Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev. 2005 Apr;85(2):495-522. doi: 10.1152/physrev.00012.2004. PMID: 15788704.
  11. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001 Dec;86(12):5992. doi: 10.1210/jcem.86.12.8111. PMID: 11739476.
  12. Jiménez-Reina, L & Cañete, Ramón & Torre, M.J. & Bernal, J.. (2002). Chronic in vivo Ipamorelin treatment stimulates body weight gain and growth hormone (GH) release in vitro in young female rats. European Journal of anatomy, ISSN 1136-4890, Vol. 6, Nº. 1, 2002, pags. 37-46. 6. 
  13. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group. Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Int J Colorectal Dis. 2014 Dec;29(12):1527-34. doi: 10.1007/s00384-014-2030-8. Epub 2014 Oct 21. PMID: 25331030.
  14. Delaney CP, Marcello PW, Sonoda T, Wise P, Bauer J, Techner L. Gastrointestinal recovery after laparoscopic colectomy: results of a prospective, observational, multicenter study. Surg Endosc. 2010 Mar;24(3):653-61. doi: 10.1007/s00464-009-0652-7. Epub 2009 Aug 18. PMID: 19688390.
  15. Gelander L, Lindstedt G, Selstam G, Wide L, Albertsson-Wikland K. Effects of acute intravenous injection of two growth hormone-releasing hormones (GHRH 1-40 and 1-29) on serum growth hormone and other pituitary hormones in short children with pulsatile growth hormone secretion. Horm Res. 1989;31(5-6):213-20. doi: 10.1159/000181119. PMID: 2515143.
  16. Sigalos JT, Pastuszak AW, Allison A, Ohlander SJ, Herati A, Lindgren MC, Lipshultz LI. Growth Hormone Secretagogue Treatment in Hypogonadal Men Raises Serum Insulin-Like Growth Factor-1 Levels. Am J Mens Health. 2017 Nov;11(6):1752-1757. doi: 10.1177/1557988317718662. Epub 2017 Aug 22. PMID: 28830317; PMCID: PMC5675260.
  17. Vittone J, Blackman MR, Busby-Whitehead J, Tsiao C, Stewart KJ, Tobin J, Stevens T, Bellantoni MF, Rogers MA, Baumann G, Roth J, Harman SM, Spencer RG. Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism. 1997 Jan;46(1):89-96. doi: 10.1016/s0026-0495(97)90174-8. PMID: 9005976.
  18. Drugs.com (2015). Sermorelin acetate. https://www.drugs.com/cdi/sermorelin-acetate.html

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