Tesamorelin

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.

Tesamorelin is a growth hormone releasing hormone (GHRH) analogue approved by the FDA for use in HIV-associated lipodystrophy. Because it increases growth hormone (GH) levels, tesamorelin can increase lean body mass, improve bone strength, burn fat, and even enhance immune function. It is the fat burning properties of tesamorelin, however, that are of greatest interest in the clinical setting. Tesamorelin is also known for its ability to improve peripheral nerve regeneration and is under investigation as a potential treatment for mild cognitive impairment (MCI). Tesamorelin has been in clinical use since 2010. Because of its long production history and relatively simple to produce characteristics, tesamorelin cost is one of the lowest among the GHRH analogues.

Purification Steps Determine Tesamorelin Cost

The cost of producing peptides generally comes from the purification and lyophilization steps of the process and not from the actual peptide synthesis. This was not always the case and producing larger peptides like tesamorelin cost quite a lot in the past. With advances in scalable synthesis, however, the production costs of many peptides have come down dramatically. This is particularly true for peptides, like tesamorelin, that require some degree of modification from their “normal” or standard counterpart[1]. In short, tesamorelin cost has declined significantly as manufacturing processes have advanced. While the purification step currently represents the bulk of the cost to manufacture tesamorelin, that is only because the cost of all of the other steps has been reduced so dramatically.

Tesamorelin and Sermorelin are both synthetic growth hormone-releasing hormone (GHRH) analogues. Sermorelin is often used as a treatment for growth hormone deficiency in both children and adults. Sermorelin works by mimicking the action of the natural hormone, growth hormone-releasing hormone (GHRH), to increase the production of growth hormone in the body. This can have various benefits, including promoting growth in children, increasing muscle mass, reducing body fat, improving sleep, and enhancing overall well-being. Sermorelin is typically administered to individuals with growth hormone deficiencies or certain medical conditions.

Tesamorelin is used primarily to treat excess abdominal fat accumulation in people living with HIV/AIDS who have developed lipodystrophy. Lipodystrophy is a condition characterized by abnormal fat distribution in the body. Tesamorelin works by stimulating the pituitary gland to release growth hormone, which can help reduce visceral fat (fat stored in the abdominal area) in these individuals. It is administered through daily injections.

Both peptides are known for their ability to bring about changes in body composition, and both have been linked to improvements in heart health and cognitive function in mouse models. Despite their similarities, however, there are unique differences between these peptides. Understanding the subtleties that arise between these two very similar peptides is helping researchers to better understand physiologic pathways and develop better, more advanced therapeutics.

Tesamorelin vs Sermorelin | A Note on Growth Hormone

Researchers have shown interest in growth hormone (GH) therapy as an alternative approach to address body composition independently of the androgen-dependent gonadal axis. Studies have demonstrated that GH therapy can yield positive effects, including increased lean body mass, reduced adiposity, and improved serum lipid profiles. Despite these promising results, the use of GH therapy remains a subject of controversy and is subject to strict regulation. Potential side effects include joint stiffness, radiculopathy, edema, and a theoretically suggested but unproven increased risk of malignancy. The issue with direct GH supplementation is that it can easily lead to overdose. The body lacks a direct feedback mechanism for regulating GH levels and instead regulates the entire GH axis at the levels of synthesis and secretion. Given the benefits of GH, researchers began seeking alternative ways to stimulate GH release to avoid the potential problems associated with direct GH supplementation.

The result of these efforts was the development of a new class of peptides referred to as growth hormone secretagogues. Growth hormone secretagogue therapy has emerged as a promising substitute for GH therapy. These compounds exhibit numerous favorable effects similar to GH therapy but without the associated adverse side effects or regulatory issues. Growth hormone secretagogues stimulate the body’s own release of GH. This stimulation occurs either through direct mimicry of growth hormone release hormone (GHRH) or interactions with ghrelin/growth hormone secretagogue receptors (GHS-R), distinct from the conventional hypothalamic-pituitary-somatotropic axis. This article focuses on the growth hormone-releasing hormone (GHRH) analogues Tesamorelin and Sermorelin.

Research indicates that GHS treatment can elevate serum GH and IGF-1 levels to levels comparable to those achieved with recombinant GH therapy, resulting in similar reductions in fat and increases in lean muscle mass. Remarkably, specific GHS can uniquely induce the natural pulsatile secretion of GH observed in vivo. This stands in contrast to exogenous GH therapy, which often leads to sustained supraphysiological levels of GH in the bloodstream[1]. As a result, the administration of GHS has the potential to offer many of the same advantages traditionally associated with GH therapy while carrying substantially lower risks.

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.