Research

Sermorelin vs Ipamorelin and Tesamorelin

Sermorelin, Ipamorelin, and Tesamorelin are all peptides that stimulate the release of growth hormone (GH) in the body, but they have some differences in terms of their mechanisms of action and thus the overall effects that they cause. Sermorelin is a synthetic peptide that works by stimulating the secretion of growth hormone-releasing hormone (GHRH) from the hypothalamus. GHRH, in turn, triggers the release of growth hormone from the pituitary gland. Sermorelin is well known for extending growth hormone peaks and increasing growth hormone trough levels. It generally does not increase GH peaks, meaning it does not cause supraphysiologic levels of GH.Ipamorelin is a synthetic peptide that specifically targets the ghrelin/growth hormone secretagogue receptor. It stimulates the release of growth hormone directly from the pituitary gland. It is known for causing very large spikes in GH levels, well above normal physiologic peaks. It is a short-lived peptide, however, and so the GH spikes are short-lived as well.Tesamorelin is a synthetic peptide that is similar in structure to human growth hormone-releasing hormone (GHRH). It stimulates the release of growth hormone from the pituitary gland. Tesamorelin is used clinically for reducing adiposity (fat tissue) and is more similar to Sermorelin than it is to Ipamorelin. Like Sermorelin, it extends the length of time that GH peaks last, but does not generally cause supraphysiologic GH levels.Sermorelin and Tesamorelin are the most similar, but it would be mistake to conflate the properties of these two peptides. Despite the fact that both are GHRH analogues and thus stimulate the release of GH from the anterior pituitary, there are profound differences in overall outcomes produced by these peptides. Whereas Tesamorelin tends to produce weight loss via targeting of fat mass, Sermorelin tends to favor muscle building and balanced fat burning resulting in body composition change, but not necessarily a huge change in weight.These differences are just one example of how peptides from the same class can differ from one another based on simple structural changes made to their amino acid sequences. Researchers have, for years now, been investigating how these subtle changes influence target effects, half-life, off-target effects, bioavailability and other features of these peptides. Now, with enough different growth hormone regulators on the market, research is starting to shift to investigate how combinations of these peptides stack up to one another. Here is a look at how Sermorelin on its own might compare to a combination of Ipamorelin and Tesamorelin. 

Sermorelin vs Ipamorelin and Tesamorelin | Growth Hormone Profiles

The primary action of all of these peptides is to influence levels of circulating growth hormone. Tesamorelin and Sermorelin do this by acting on the GHRH receptor while Ipamorelin influences GH levels by acting on the ghrelin or growth hormone secretagogue receptor (GHS-R). The receptors that these peptides target in addition to how they bind to their specific receptors determines their impact on growth hormone levels.

Sermorelin is very similar in structure to GHRH and thus is similar in function as well. Research shows that Sermorelin can lead to an increase in GH with peak levels occurring about 30 minutes to a few hours after administration. On average, studies have reported GH increases in the range of 2 to 10 times the baseline GH levels following Sermorelin administration, with once-daily administration resulting in increases that are on the lower end of that spectrum. One of the benefits of using Sermorelin is that it promotes a natural, pulsatile release of GH. The body’s natural GH secretion occurs in a pulsatile fashion, with several peaks and troughs throughout the day. Sermorelin therapy aims to replicate this pattern, which is essential for the body’s overall growth and maintenance. Maintenance of pulsatile GH release is one of the primary keys to avoiding off-target effects.

Ipamorelin is a ghrelin mimetic and as such binds to the GHS-R. In clinical and research studies, Ipamorelin has been shown to increase GH levels, but the magnitude of the increase can vary. Typically, after the administration of Ipamorelin, there is a rapid spike in GH levels, and this peak can reach levels several times higher than baseline. Of the three peptides here, Ipamorelin is the most likely to cause massive, but short-lived increases in GH levels. This, of course, makes Ipamorelin useful when targeted GH peaks need to be timed with something like exercise, food intake, or sleep.

The increase in GH levels after Ipamorelin administration tends to be dose-dependent, meaning that higher doses are generally associated with a more significant GH response. The frequency and timing of Ipamorelin administration can also influence GH release. As a short-acting peptide, Ipamorelin can be dosed more frequently than Sermorelin to achieve net increases in GH levels. This is made possible not just by Ipamorelin’s short half-life, but by its near total lack of off-target effects. Ipamorelin is widely regarded in research circles as the most specific of the growth hormone secretagogues and as having the fewest off-target effects.

Tesamorelin is a GHRH analogue. Studies of Tesamorelin have shown that it can lead to an increase in growth hormone levels and this increase is generally within a physiologically normal range. The specific increase in GH levels can depend on factors such as the individual’s baseline GH levels, the dosage of Tesamorelin administered, and the duration of treatment. Like Sermorelin, Tesamorelin can help to preserve the normal pulsatile pattern of GH release from the pituitary gland, acting to extend the duration of GH peaks while having less effect on peak GH levels.

Ipamorelin for Weight Loss: What to Know in 2024

Ipamorelin is a synthetic growth hormone secretagogue receptor agonist, which makes it like the natural peptide hormone ghrelin. As an analogue of ghrelin, ipamorelin is a potent stimulator of growth hormone secretion. It is also among the most selective of the ghrelin mimetics, which means ipamorelin has few unintended side effects. Ipamorelin has been studied for its ability to stimulate bone formation and as a potential treatment for post-operative ileus. It is also of interest in weight loss research for its ability to modify GH secretion, impact insulin release, and alter food intake.

Ipamorelin for Weight Loss

There has been a lot of research into using ipamorelin for weight loss, but this can be confusing given the fact that ghrelin, from which ipamorelin is derived, is often referred to as the hunger hormone. If a hormone stimulates appetite, how can it possibly be useful in weight loss? The answer to this question lies in how ipamorelin stimulates appetite and how the peptide alters energy balance to favor lean body mass as opposed to fat mass. The answer also lies in the intelligent use of ipamorelin which, when paired with proper diet and conditioning, can lead to profound fat burning.

Using ipamorelin for weight loss might be more accurately referred to as using ipamorelin for promoting leaning body mass. Ipamorelin is a potent growth hormone secretagogue. And growth hormone is known for stimulating growth, hence the name! Growth hormone (GH) does not simply stimulate growth in general, but rather stimulates the growth of lean body tissues like muscle and bone. It stimulates the burning of fat. So, increasing GH hormone levels helps to build muscle and bone density while reducing adipose (fat) tissue.

Ipamorelin and CJC-1295 are amongst the most heavily researched growth hormone secretagogues. While ipamorelin acts at the ghrelin receptor, CJC-1295 acts at the growth hormone releasing hormone (GHRH) receptor. This fact alone makes the combination of these peptides popular in research investigating how both high and widened growth hormone (GH) peaks might work synergistically to produce enhanced effects while limiting side effects. Fortunately, the Ipamorelin/CJC-1295 cost point remains low because both peptides are well established and therefore affordable.

Ipamorelin Sleep Research

Ipamorelin sleep research is a branch of ipamorelin research that focuses on how this peptide (and any ghrelin analogue) can improve sleep. Research has shown that ghrelin plays a peripheral but important role in sleep and that this role may be linked to both mood disorders like depression as well as obesity. Uncovering the link could provide insight into a common mechanism between these conditions. Ipamorelin may seem like an odd choice for sleep research, but it makes perfect sense when you consider the interconnection between sleep and energy homeostasis (e.g., growth hormone release is tied to sleep cycles). In fact, energy homeostasis seems to be at the core of a lot of human biology and gaining a deeper understanding of it can only serve to improve our understanding of our overall functioning.

Ipamorelin vs GHRP-2

Many people think that ipamorelin and GHRP-2 are the essentially the same thing. After all, both cause an increase in the secretion of growth hormone (GH). In reality, ipamorelin and GHRP-2 are very different peptides and the fact that they cause GH hormone release is the only thing they really share in common. Below is summary of ipamorelin vs GHRP-2 that outlines the similarities, differences in their respective research studies.

Both ipamorelin and GHRP-2 cause the pituitary gland to release more growth hormone by binding to the growth hormone secretagogue receptor. This means that both peptides are analogues of ghrelin. Ghrelin, a naturally occurring peptide produced in the gastrointestinal tract, is often referred to as the hunger hormone as it stimulates eating behavior. It does so much more than that though.Growth Hormone Releasing Hormone (GHRH).Stimulation of the growth hormone secretagogue receptor (GHS-R) has effects on learning, memory, the sleep-wake cycle (diurnal cycle), reward behavior, glucose metabolism, and even taste sensation. Most importantly, stimulating this receptor impacts energy balance in the body, helping to shift the body from catabolism (the breakdown of stored energy) to anabolism (the storage of energy and the repair and building of muscle and other tissue). This shift occurs via the stimulation of GH release. GHS-Rs are found on both the hypothalamus and the pituitary gland, which means that peptides like ipamorelin and GHRP-2 have a two-pronged approach for stimulating growth hormone release. The first is via direct stimulation of the pituitary gland where GH is stored and the second is via the release of GHRH, which has its own receptors on the pituitary gland for stimulating GH release.

What Is Ipamorelin?

In the world of anti-aging research, a handful of peptides have become superstars. Ipamorelin is one of those peptides. This short peptide is just five amino acids in length, but is one of the most selective growth hormone secretagogue receptor agonists known. This means that ipamorelin research has been shown to help build lean body mass and fight obesity without having unwanted effects on other aspects of the body like hair growth or decreased sexual function[1].

Ipamorelin is a peptide, which means it is made of the same amino acid building blocks found in all proteins. Ipamorelin falls into the subcategory of anti-aging peptides as well as into the subcategory of fat-burning peptides. In animal studies, it has been shown to effectively fight the signs of aging while benefiting muscle growth, bone health, and GI system function.

Because of its relative lack of secondary effects, ipamorelin is often referred to as the gentle growth hormone releasing peptide. This is because, when compared to other peptides like Sermorelin or GHRP-6, Ipamorelin tends to only affect the growth hormone axis. This makes it particularly useful in research exploring the isolated effects of growth hormone secretagogue agonists.

Sermorelin vs Ipamorelin: Structure and Route of Administration

Sermorelin is made up of the first 29 amino acids from the much larger, naturally occurring GHRH peptide. It is the smallest fraction of GHRH than retains all of the properties of the parent molecule. Weighing in at 3357.9 g/mol, Sermorelin is a relatively large, heavy peptide that must be injected sub-cutaneous to be absorbed. It is not orally bioavailable. As a result of its large size, Sermorelin has a more significant three-dimensional structure than Ipamorelin and is thus is a little less stable in terms of storage half-life.

Source: PubChem

Ipamorelin is substantially smaller than Sermorelin at just 5 amino acids and 711.868 g/mol. It is a derivative of GHRP-1, which is itself a derivative of met-enkephalin. Though the most common route of administration for Ipamorelin is via sub-cutaneous injection, the peptide is also orally active and can even be absorbed though the nasal mucosa.

Source: PubChem

Ipamorelin vs Sermorelin: Lean Body Mass

Both Sermorelin and Ipamorelin favor the development of lean body mass over fat mass, but Sermorelin is the more potent of the two. This arises from the fact that Sermorelin is both a growth stimulator and a fat burner while Ipamorelin is a more general growth stimulator. That is not to say that Ipamorelin isn’t effective, it is, but ipamorelin isn’t as strictly favorable of lean body mass deposition as Sermorelin. This difference arises from the fact that Ipamorelin is a ghrelin analogue and ghrelin favors food intake in general. Its growth hormone boosting properties shift the overall balance away from fat deposition and toward lean body mass deposition, but the Ipamorelin peptide is best thought of as a general weight boosting peptide while Sermorelin is best thought of as a more exclusive booster of lean body mass. In fact, Sermorelin is often referred to as a lipolytic or fat-burning peptide.

Both peptides stimulate the development of bone and other connective tissue, but Ipamorelin appears to have the advantage in this realm. In fact, ipamorelin is so effective in boosting bone density and mineralization that it has been investigated as a potential treatment for corticosteroid-induced bone loss as well as osteoporosis[7], [8].

When it comes to muscle growth, Sermorelin is probably the big winner, though this can be debated endlessly. Sermorelin not only boosts muscle hypertrophy and hyperplasia, it reduces fat mass and thus causes a shift in body chemistry toward lean body weight. In other words, Sermorelin will always favor the production of lean body mass even if diet is not perfectly geared toward muscle development. Ipamorelin, on the other hand, is more of a mixed bag. It will always cause muscle growth, but ipamorelin may channel some of those calories into fat deposition as well.

Tesamorelin and Ipamorelin are both peptide-based therapeutics that belong to the class of growth hormone-releasing peptides (GHRPs). They are used for different purposes and have distinct receptor binding properties, but because they both affect natural growth hormone (GH) levels, they have similar effects in many respects. Both peptides have seen renewed research interest, however, thanks to a boom in the weight loss field led by peptide compounds like semaglutide and liraglutide. While both Tesamorelin and Ipamorelin are associated with changes in body composition, fat mass, and lean body mass, there is a great deal more to what these peptides can do.

Tesamorelin vs. Ipamorelin: Properties

Tesamorelin is approved for the treatment of HIV-associated lipodystrophy. This very narrow approval belies the peptide’s wider use as an agent for altering body composition. Research indicates that Tesamorelin can reduce fat mass, boost muscle and bone mass, improve peripheral nerve regeneration, and may even be useful in the treatment of mild cognitive impairment.

Ipamorelin, which underwent phase II clinical trials for the treatment of postoperative ileus, is known to be the most selective ghrelin receptor (aka growth hormone secretagogue receptor/GHSR) agonist yet discovered. It increases plasma growth hormone levels in animals but has no effect on prolactin, follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, or adrenocorticotropic hormone levels. The astounding specificity of Ipamorelin makes it a highly useful peptide for studying the effects of increased GH levels with confounding results by elevating levels of other hormones.

MK677 and Ipamorelin are both selective agonists of the ghrelin receptor. Ipamorelin is a peptide analogue of ghrelin whereas MK677 is an unusual molecule that doesn’t fit into any specific category (it isn’t a peptide). These two compounds, while affecting a similar receptor, have different properties and produce different biochemical results. Many people are interested in the differences between MK677 vs Ipamorelin. Below is a look at how these compounds differ as well as how they are alike.

MK677 vs Ipamorelin

MK677, also known as Ibuatmoren and Oratrope, is an orally active, non-peptide, selective agonist of the ghrelin receptor. MK677 shares no structural similarities with ghrelin and therefore no structural similarities with Ipamorelin. Research shows that MK677 increases the secretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) without affecting cortisol levels. It is currently under investigation for the treatment of growth hormone deficiency, muscle wasting, bone wasting, and appetite stimulation. MK677 has a long half-life and once-daily dosing in most trial settings.

Ipamorelin is a peptide analogue of ghrelin that stimulates the secretion of GH. It is among the most selective of ghrelin analogs with research revealing no effect on ACTH, prolactin, follicle-stimulating hormone, luteinizing hormone, thyroid stimulating hormone, or cortisol levels. Ipamorelin has been investigated in the treatment of GH deficiency, muscle wasting, and post-surgical ileus. It has also been the subject of numerous clinical trials for its ability to increase bone strength and mineralization.