Tesamorelina is a synthetic analog of growth hormone-releasing hormone (GHRH), which acts on the pituitary gland and stimulates the secretion of endogenous growth hormone (GH). The substance was approved by the U.S. Food and Drug Administration (FDA) in 2010 for the reduction of excess subcutaneous fat in adults living with HIV and lipodystrophy. It is known by the trade name Egrifta, among others.
From a chemical point of view, tesamorelina is an analog of human GHRH, composed of 44 amino acids. Its N-terminus contains a chemical modification aimed at increasing the stability of the molecule compared to the natural hormone.
After binding to GHRH receptors in the pituitary gland, tesamorelina stimulates the secretion of growth hormone. Subsequently, there is an increase in the concentration of insulin-like growth factor 1 (IGF-1), which is involved in the regulation of cell growth, metabolism, and other physiological processes.
The most clinical data regarding tesamorelin come from studies on excessive accumulation of visceral adipose tissue in people with HIV. Scientists also analyzed its impact on liver fat content, metabolic parameters, body composition, muscle function, and selected cognitive indicators.
The results of these studies do not, however, mean that tesamorelina has proven efficacy in all the areas analyzed. The individual applications differ in terms of the level of evidence, the size of the populations studied, and the regulatory status.
What is tesamorelina and how does it work?
Tesamorelin belongs to the GHRH analogues, which are substances that mimic the action of the growth hormone-releasing hormone.
Natural GHRH is produced in the hypothalamus and is one of the main regulators of GH secretion by the pituitary gland. Growth hormone influences lipid metabolism, energy metabolism, and the activity of many tissues.
In response to the GH signal, the production of IGF-1 also increases, primarily in the liver. IGF-1 is involved in growth and metabolic processes, but its elevated concentration is not automatically beneficial. For this reason, it is also an important safety parameter in studies involving substances that affect the GH–IGF-1 axis.
Unlike the direct administration of growth hormone, tesamorelina acts earlier in the hormonal regulation process by stimulating its secretion by the pituitary gland.
However, this does not mean that its action is limited solely to adipose tissue. Changes in the activity of the hormonal axis can also affect the glucose metabolism, fluid retention, and other physiological processes.
What have clinical studies on tesamorelin shown?
Studies on tesamorelin focused primarily on changes in the visceral adipose tissue, which is located deep in the abdominal cavity, around the internal organs.
Some people living with HIV experience disorders in the distribution of fat tissue, known as lipodystrophy. These can include an increase in visceral fat, a decrease in subcutaneous fat, or the presence of both conditions.
Clinical studies have shown that tesamorelina can reduce the amount of visceral adipose tissue in this population. In some studies, changes in triglyceride levels, liver fat content, and other metabolic markers were also observed.
However, the conclusions regarding the prevention of cardiovascular diseases, the improvement of cognitive function, and the long-term reduction of the risk of liver cancer remain significantly less certain.
In these areas, researchers primarily evaluated indirect indicators rather than always the actual clinical events.
Tesamorelina and the fat content in the liver
Study by Fourman et al. (2020)
Fourman and colleagues analyzed the effect of tesamorelin on molecular changes in the liver in people living with HIV and nonalcoholic fatty liver disease (NAFLD).
The study included 61 participants who were observed for 12 months.
Not only the amount of liver fat was evaluated, but also the activity of genes related to lipid metabolism, mitochondrial function, inflammation, and fibrosis processes.
The results indicated changes in the expression of genes involved in lipid metabolism and mitochondrial function. It was also noted that the activity of certain pathways related to inflammation and fibrosis was reduced.
The authors also drew attention to changes in the expression of genes associated with biological processes essential for the development of hepatocellular carcinoma.
However, this is not equivalent to demonstrating that tesamorelina prevents liver cancer. Gene expression analysis allows identifying potential mechanisms, but it does not replace long-term studies on the actual frequency of tumors.
Study by Fourman et al. (2017)
The analysis published in 2017 used data from two Phase III clinical trials involving a total of 806 adult HIV-infected individuals.
The researchers examined whether the reduction in the amount of visceral adipose tissue is associated with changes in the activity of the liver enzymes ALT and AST.
In participants with elevated baseline values who achieved at least an 8% reduction in visceral fat, a decrease in ALT of approximately 8.9 U/L and AST of approximately 3.8 U/L was observed.
The results indicated a relationship between the reduction in the amount of adipose tissue and an improvement in selected laboratory parameters of the liver.
However, they do not prove that a similar effect occurs in all people with liver diseases, regardless of HIV infection and other clinical factors.
Study by Stanley et al. (2019)
Stanley and colleagues conducted a randomized double-blind study involving 61 people with HIV and confirmed liver steatosis.
The participants received tesamorelin or a placebo for 12 months. Subsequently, an additional observation period was scheduled.
In the tesamorelin group, an average reduction in liver fat content of approximately 4.1 percentage points was observed, corresponding to a relative reduction of approximately 37%.
After one year, the liver fat content below 5% was achieved by about 35% participants taking tesamorelin, compared with about 4% in the placebo group.
The study also provided data on fiber markers and glucose metabolism.
The results indicate the possibility of influencing the fat content in the liver in a specific group of patients. However, they do not confirm the overall effectiveness of tesamorelin in all forms of fatty liver disease.
Tesamorelin and adipose tissue in people with HIV
Study by Stanley et al. (2014)
In a six-month study, 50 adults living with HIV were evaluated; they had increased accumulation of fat tissue in the abdominal cavity.
28 participants were assigned to the tesamorelin group, and 22 people to the placebo group.
In the group receiving tesamorelin, a mean reduction in the surface area of adipose tissue was observed by approximately 34 cm². In the placebo group, an increase of approximately 8 cm² was observed.
At the same time, the median percent change in liver fat content was approximately −2.0 percentage points in the tesamorelin group and +0.9 percentage points in the placebo group.
The study indicated that the effect of tesamorelin may involve both the abdominal fat tissue and the fat content in the liver.
Study by Falutz et al. (2010)
Falutz and colleagues evaluated the long-term outcomes of treatment in 404 adult people living with HIV who had excess subcutaneous fat tissue.
After six months in the tesamorelin group, there was a reduction in its amount of about 11%, corresponding to a surface change of about 21 cm².
A reduction in waist circumference and an improvement in the waist-to-hip ratio were also observed.
Over the longer term, participants who continued treatment reported a reduction in fat tissue of approximately 18%.
After discontinuation of therapy, the amount of subcutaneous fat tissue increased again.
This result is important in interpreting the durability of the observed effect. It indicates that the change in body composition does not have to persist after the pharmacological effect has ended.
Overall analysis by Falutz et al. (2010)
The analysis of two multicenter Phase III studies included 806 participants.
After 26 weeks in the tesamorelin group, a mean reduction in visceral adipose tissue was observed of approximately 15.4% compared to the placebo group.
The researchers also noted changes in selected lipid markers, including a decrease in triglyceride levels of about 12.3% and in the total cholesterol to HDL ratio of about 7.2%.
In the assessments of the participants and doctors, a reduction in the discomfort associated with the appearance of the abdomen was also described.
In people who continued therapy, the changes were observed to persist until 52 weeks.
However, it is worth distinguishing between an improvement in metabolic markers and a confirmed reduction in the number of heart attacks, strokes, or other cardiovascular events. The study did not directly resolve these issues.
Analysis by Mangili et al. (2015)
Mangili and colleagues used data from studies involving 806 people living with HIV.
The aim of the analysis was to determine the factors related to the response to tesamorelin.
A reduction in the amount of visceral adipose tissue was observed in different subgroups, but the magnitude of the response was not uniform.
Larger changes were described among some participants with metabolic syndrome, elevated lipid levels, and other metabolic factors.
The probability of achieving a surface area of adipose tissue below 140 cm² was also analyzed.
The results show that the participants' baseline characteristics may be important for the observed response. However, this does not mean that a single parameter allows for reliable prediction of the outcome for a particular individual.
Study by Falutz et al. (2008)
The study involving 410 participants evaluated the persistence of changes in body composition over a period of up to 52 weeks.
Individuals who continued taking tesamorelin maintained reduced amounts of visceral adipose tissue. In one of the analyses, the reduction after one year was approximately 18%.
In participants who discontinued treatment, a recurrence of increased visceral fat was observed.
The study also analyzed lipid parameters and glucose metabolism.
The results provided information about the durability of the response during therapy, but do not prove that long-term treatment is appropriate for every patient.
Review by Mateo et al. (2011)
Mateo and colleagues presented an overview of data regarding tesamorelin in HIV-associated lipodystrophy.
The authors described disorders of adipose tissue distribution, in which the excessive accumulation of visceral fat may be accompanied by a loss of subcutaneous tissue.
In the analyzed studies, tesamorelina primarily reduced the amount of visceral fat, with relatively limited changes in subcutaneous fat tissue.
The review also drew attention to lipid parameters, body image assessment, and the return of visceral fat after the end of treatment.
Study by Falutz et al. (2007)
The study published in 2007 involved 412 adults living with HIV and an increased amount of fat tissue in the abdomen.
After 26 weeks in the group receiving the GHRH analog, a reduction in visceral fat tissue of approximately 15% was observed.
A reduction in triglyceride levels was also observed, as well as a change in the ratio of total cholesterol to HDL.
These results were among the important clinical data indicating the effect of stimulation of the GHRH–GH axis on the distribution of adipose tissue in people with HIV.
Analysis by Rahman et al. (2023)
Rahman and colleagues evaluated data from a Phase III study by comparing people with accumulation of fat tissue in the cervical region with participants without this characteristic.
The accumulation of fat in this area is popularly referred to as „bellowing the neck”.
In both subgroups, a decrease in visceral adipose tissue of approximately 8% was observed.
The changes in waist circumference, the amount of body fat, and the lean body mass had an approximate direction.
The results suggest that the presence of additional accumulation of adipose tissue in the cervical region does not preclude a response in the visceral fat area.
Study by Falutz et al. (2005)
In a 12-week placebo-controlled study, 61 people living with HIV and with excess abdominal fat participated.
The researchers compared different levels of exposure to the GHRH analog and the placebo.
In the active treatment groups, the IGF-1 concentration increased by approximately 48% and 65%, respectively, compared to placebo.
In the group with greater exposure, there was a reduction in the trunk fat mass of approximately 9.2 % and in the visceral fat mass of approximately 15.7%.
In the group with lower exposure, the reduction in trunk fat was about 4.6%.
Changes in non-fat mass and lipid parameters were also observed.
These results provided early data on the relationship between exposure to the substance, hormonal response, and changes in body composition. They should not be considered as instructions for dose selection.
Tesamorelina and muscle parameters
Study by Adrian et al. (2019)
Adrian and his colleagues analyzed data from previous clinical studies, focusing on parameters of the trunk muscles.
193 participants who had at least an 8 percent reduction in visceral fat were compared with 148 people in the placebo group.
Computer tomography was used for the evaluation.
In the group responding to tesamorelin, the density of selected muscle groups was increased by approximately 1.56–4.86 units compared to placebo.
There was also a slight increase in muscle area, amounting to approximately 0.64–1.08 cm² in the analyzed groups.
In the case of the rectus abdominis and the greater trochanter muscle, larger changes in surface area were described as being of the order of 0.44–0.46 cm².
These changes may indicate differences in the composition and characteristics of muscle tissue. However, they are not direct evidence of improvement in muscle strength, physical performance, or functional fitness.
Tesamorelina and the functioning of mitochondria
Study by Makimura et al. (2014)
Makimura and colleagues conducted a 12-month study involving 39 adults with obesity and reduced secretion of growth hormone.
The researchers evaluated, among other things, changes in IGF-1 levels and parameters related to mitochondrial function.
In the group receiving tesamorelin, an increase in IGF-1 was noted of approximately 102.9 µg/l, compared to an increase of approximately 22.8 µg/l in the placebo group.
Higher IGF-1 levels were associated with better results in measurements of phosphocreatine recovery, which is used to assess muscle energy metabolism.
The results suggest a relationship between the activity of the GH–IGF-1 axis and selected parameters of mitochondrial function.
However, they do not automatically confirm an increase in the subjectively perceived energy or an improvement in overall body performance.
Tesamorelina and lipids, glucose and metabolic parameters
Study by Stanley et al. (2012)
Stanley and colleagues analyzed data from two Phase III clinical trials.
People who achieved at least an 8 percent reduction in visceral fat tissue were compared with participants whose response was less significant.
In people with greater reduction of visceral fat, more favorable changes in triglyceride levels and selected metabolic markers were observed.
Glycemia, hemoglobin A1c and adiponectin were also analyzed.
In the studied group, no clear deterioration of any of the indicators of the glucose economy was observed.
This does not mean that tesamorelina is devoid of influence on the risk of hyperglycemia. The metabolic safety assessment requires taking into account both the average results of the studies and the adverse effects occurring in individual participants.
Tesamorelina and the activation of the immune system
Study by Stanley et al. (2021)
In a study involving 61 people living with HIV and fatty liver disease, changes in selected markers of immune activation were evaluated.
The scientists analyzed blood samples and data on gene activity in the liver tissue.
After the observation period, a reduction was observed in some markers associated with T-lymphocyte activation and inflammatory response.
Changes in the expression of genes involved in hepatic immune pathways were also observed.
The results suggest that the effect on the GHRH–GH axis may be associated with changes in immunological signaling under certain clinical conditions.
However, they do not prove that tesamorelina constitutes a general anti-inflammatory or immunomodulatory therapy.
Tesamorelin and cardiovascular risk indicators
Study by Makimura et al. (2012)
In a randomized study involving 60 adults with obesity and reduced growth hormone secretion, the effects of a GHRH analog on body composition and selected cardiovascular risk factors were evaluated.
In the active treatment group, a reduction in the amount of subcutaneous fat tissue was observed.
The researchers also analyzed the thickness of the intima-media complex, the concentration of triglycerides and C-reactive protein (CRP).
The results indicated changes in some indicators related to metabolic and cardiovascular risk.
However, they were not sufficient to demonstrate a reduction in the incidence of heart attacks, strokes, or cardiovascular deaths.
Study by Stanley et al. (2011)
Stanley and colleagues evaluated data from 410 people living with HIV and having excessive amounts of visceral fat.
The relationships between changes in adipose tissue volume and markers of inflammation, fibrinolysis, and metabolic activity were analyzed.
The reduction in visceral fat was associated with changes in selected markers, including those related to the tissue activator plasminogen activator (tPA) and adiponectin.
However, changes in the concentration of fibrinolysis markers should not be confused with direct evidence of a reduction in the risk of thrombosis.
The results are primarily important for understanding the relationship between adipose tissue and inflammatory and metabolic processes.
Analysis by Grinspoon et al. (2025)
In the analysis of data from Phase III studies involving 543 HIV-infected individuals, the effect of tesamorelin on the predicted cardiovascular risk was evaluated.
After 26 weeks, a small reduction in the estimated 10-year risk of cardiovascular disease was observed, amounting to approximately 0.40 percentage points.
The change was more noticeable in participants with a higher baseline risk.
The differences in lipid parameters were of primary importance.
However, the result was a model estimate of risk, not a directly observed reduction in cardiovascular incidents.
Tesamorelin and HIV therapy based on integrase inhibitors
Study by Russo et al. (2024)
Russo and colleagues analyzed data from HIV and fatty liver disease participants, focusing on individuals receiving integrase inhibitors (INSTI).
Of the 61 participants in the study, 38 used an INSTI-based therapy.
In the analyzed subgroup, 15 people received tesamorelin and 16 received placebo for 12 months.
In the tesamorelin group, an average reduction in the surface area of the subcutaneous adipose tissue was recorded by about 25 cm², while in the placebo group an increase of about 14 cm² was observed.
The fat content in the liver decreased on average by about 4.2 percentage points in the active treatment group, compared with about 0.5 percentage points in the placebo group.
The proportions of body fat in the trunk and limbs were also analyzed, as well as safety parameters.
The results indicate that changes in body composition were also observed in this subgroup of people receiving antiretroviral therapy.
However, due to the small size of the subgroup, their scope and the possibility of generalization should be interpreted with caution.
Tesamorelina and cognitive functions
Study by Baker et al. (2012)
Baker and colleagues conducted a 20-week randomized, controlled, placebo trial involving 152 older adults.
Among the participants were 86 people without recognized cognitive disorders and 66 people with mild cognitive impairment (MCI).
Performance functions, verbal memory, visual memory and other aspects of cognitive performance were assessed.
In the group receiving the GHRH analog, improvements were observed in some indicators of cognitive functioning, especially executive functions.
Changes in verbal memory have also been noted.
In the study, the IGF-1 concentration increased by about 117%, and the amount of adipose tissue decreased by an average of about 7.4%.
In participants with MCI, an increase in fasting insulin levels of approximately 35% was also observed.
Mild adverse reactions were reported more frequently in the active treatment group than in the placebo group, respectively in approximately 68% and 36% participants.
The results indicate an interesting direction for research into the GHRH–GH axis and brain aging. However, they do not prove that tesamorelina prevents dementia or constitutes an approved treatment for cognitive disorders.
Study by Friedman et al. (2013)
Friedman and colleagues analyzed changes in selected brain metabolites in 30 participants, including 17 people with MCI and 13 people without cognitive impairment.
The study lasted 20 weeks.
Measurements were taken at the beginning, in the 10th and 20th weeks, analyzing, among other things, the anterior frontal ridge, the rear part of the ring vertebra, and the posterior caudal vertebrae.
An increase in the level of gamma-aminobutyric acid (GABA) was observed in the brain areas studied.
An increase in N-acetylaspartylglutamine (NAAG) was also observed in the anterior horn-lateral cortex.
Meanwhile, in the rear part of the turn, the level of myo-inositol, a metabolite used, among other things, in studies of degenerative changes and neurological processes, decreased.
No significant change in the level of glutamate was observed.
The results suggest that hormone axis modulation can affect selected neurochemical parameters.
However, changes in metabolites do not constitute independent evidence of improved brain health, inhibition of neurodegeneration, or efficacy in Alzheimer's disease.
Study by Ellis et al. (2025)
In a six-month open-label study, 73 people living with HIV with abdominal obesity and cognitive impairment were evaluated.
A group receiving tesamorelin was compared with standard care.
A reduction in waist circumference of approximately 2.7 cm was observed in the tesamorelin group compared to the control group.
However, no statistically significant advantage was shown in terms of improving cognitive functions.
The increase in IGF-1 levels was also not consistently associated with improved cognitive performance.
This study highlights an important limitation of previous observations: beneficial hormonal and metabolic changes do not necessarily translate into a measurable improvement in brain function.
Pharmacokinetics of tesamorelin
Pharmacokinetics describes the processes of absorption, distribution, and elimination of substances from the body.
In the case of tesamorelin, studies showed relatively low absolute bioavailability after subcutaneous administration, amounting to less than 4%.
This does not mean that the substance is biologically inactive. Its action depends on its interaction with receptors and the activation of the hormonal response.
In pharmacokinetic analyses, volume of distribution values of approximately 9.4 l/kg were reported in healthy participants and 10.5 l/kg in HIV-infected individuals.
The reported half-life was approximately 26 minutes in healthy individuals and 38 minutes in HIV-infected participants.
The estimated plasma clearance is approximately 1060 l/h.
In the population pharmacokinetic study, no significant effect of some of the analyzed demographic and clinical characteristics was found on the basic parameters of exposure.
After 14 days of repeated exposure, a slight change in bioavailability was observed, estimated at approximately 13%.
The exact metabolic pathways of tesamorelin have not been fully characterized in formal human studies. Due to its peptide structure, enzymatic breakdown of peptide bonds is assumed to be involved.
Pharmacokinetic parameters do not constitute an independent basis for determining the method of administration of the substance outside the approved product documentation.
Regulatory status of tesamorelin
On November 10, 2010, the FDA approved tesamorelin under the name Egrifta for the reduction of excess abdominal fat in adults living with HIV and lipodystrophy.
The product was developed by the Canadian company Theratechnologies.
In the United States, various commercial formulations of tesamorelin were available, including Egrifta SV.
The approval applies to a specific clinical indication. It does not mean that tesamorelin is automatically approved for the treatment of general obesity, improving athletic performance, preventing aging, or treating cognitive disorders.
The registration status, product characteristics, and requirements for use may vary between countries and change over time.
Dosage of tesamorelin in clinical studies
In many of the cited clinical studies, a regimen of 2 mg of tesamorelin per day was used. Other exposure levels were also evaluated in previous studies.
The studies usually lasted from several weeks to 6–12 months, depending on the purpose and the project.
The data regarding doses should be interpreted as a description of the research methodology, not as a universal instruction for use.
Not all tesamorelin preparations are equivalent in terms of formulation, method of preparation, and approved product information.
Therefore, historical research schemes should not be automatically transferred to other products or applications.
Safety of tesamorelin and monitoring in studies
In clinical studies, among other things, injection site reactions, joint pain, muscle pain, limb pain, and fluid retention-related swelling were reported.
Tesamorelin increases IGF-1 levels, which is directly related to its mechanism of action.
In some studies, the average glycemic parameters remained stable, but cases of glucose intolerance and hyperglycemia were also reported.
For this reason, tesamorelin cannot be considered a substance without metabolic risk.
Warnings regarding malignant tumors, hypothalamic-pituitary disorders, hypersensitivity, and pregnancy also play an important role in the documentation of medicinal products.
Safety data should always be considered in the context of the specific product, indication and patient population.
Contraindications for the use of tesamorelin
Contraindications for medicinal products containing tesamorelin have been described in the product documentation, including:
- pregnancy;
- active malignant disease;
- specific disorders of the hypothalamic-pituitary axis;
- known hypersensitivity to tesamorelin or to any of the formulation's ingredients.
In the case of hypothalamic-pituitary disorders, previous pituitary surgery, irradiation, injuries, or other damage to this structure can be significant.
Detailed contraindications and warnings should be evaluated in accordance with the current documentation of the specific registered product.
How long has the effect of tesamorelin been observed in studies?
In studies of excessive accumulation of visceral fat in people with HIV, significant changes were observed already at around 26 weeks of age.
Falutz and colleagues described a reduction in visceral fat of about 11% after six months in one of the analyses.
In the study by Stanley et al. (2014), a decrease in liver fat content was also observed at the same time horizon.
The 12-month study, including the work of Fourman and Stanley, provided additional data on liver and molecular changes.
However, this does not mean that longer exposure always leads to greater improvement or is devoid of additional risk.
The results depend on the characteristics of the participants, the endpoints, and the length of the observation period.
Storage and properties of tesamorelin formulations
The storage conditions for tesamorelin depend on the specific medicinal product and its formulation.
It should not be assumed that all lyophilized tesamorelin preparations have identical requirements regarding temperature, light, solvent, and stability after preparation.
Information regarding the storage of the lyophilized product is not automatically valid for the reconstituted solution.
The composition of the excipients, the type of diluent and the validated shelf life are also important.
More information about the general physicochemical properties of lyophilized products is presented in the article. Why are some lyophilized peptides difficult to dissolve?.
This article discusses laboratory issues and does not replace the instructions for a specific medicinal product.
How is tesamorelina administered in clinical applications?
In approved clinical applications, tesamorelina is available as a product intended for subcutaneous administration.
The details of preparation, the type of diluent, the volume and the method of administration depend on the specific formulation and the approved documentation.
It cannot be assumed that instructions applicable to one commercial form will be valid for another lyophilized material labeled with the same substance name.
These differences are important for quality, stability and safety.
Tesamorelina and ipamorelina – differences in the mechanisms of action
Tesamorelina and ipamorelina affect the secretion of growth hormone, but they act through different receptors.
Tesamorelin is an analog of GHRH and stimulates the GHRH receptor in the pituitary gland.
Imipramine, on the other hand, belongs to the group of substances that stimulate the ghrelin receptor, known as GHSR.
In experimental studies, ipamorelin was evaluated, among other things, for its selectivity of the hormonal response.
Both substances can therefore affect the GH–IGF-1 axis, but this does not mean that their clinical profiles, safety, and regulatory status are the same.
Tesamorelin has extensive clinical documentation in a specific HIV-related indication. For ipamorelin, the evidence regarding clinical uses in humans is much more limited.
No reliable randomized studies have been presented to confirm the efficacy and safety of the combined use of these two substances.
Hypotheses of synergy resulting from differences in mechanisms of action cannot replace the results of clinical studies.
Does tesamorelina affect testosterone?
Tesamorelin acts primarily through the GHRH–GH–IGF-1 pathway, rather than directly by regulating testosterone synthesis.
In the presented clinical studies, no unequivocal, direct increase in endogenous testosterone levels was observed.
The effect on body composition and metabolism does not automatically mean an effect on androgen production.
Therefore, there is no basis for presenting tesamorelin as a substance intended to increase testosterone based on these data.
Tesamorelin and testosterone replacement therapy (TRT)
Testosterone replacement therapy and tesamorelin work through different hormonal systems.
Tesamorelin stimulates GH secretion and increases IGF-1, whereas TRT aims to supplement testosterone in certain clinical conditions.
Given the different mechanisms of action, hypothetical differences in their effects on body composition, metabolism, and other parameters can be considered.
However, this does not mean that the combination of these therapies has a confirmed clinical advantage.
The presented material does not describe appropriate randomized studies that would allow for a clear assessment of the efficacy and safety of such a combination.
Both interventions require separate risk assessment. TRT can affect hematocrit, for example, while tesamorelina increases IGF-1 and can affect glucose metabolism.
Therefore, their simultaneous use should not be presented as a proven strategy for improving body composition or „hormonal optimization”.
Tesamorelina and AOD-9604 – scientific comparison
Tesamorelina and AOD-9604 are peptide substances studied in the context of fat metabolism, but they differ in structure and mechanism of action.
Tesamorelin is an analog of GHRH that stimulates the secretion of endogenous growth hormone and increases the concentration of IGF-1.
AOD-9604, on the other hand, is a fragment of the growth hormone molecule developed to study specific metabolic effects without reproducing the full hormonal profile of GH.
For tesamorelin, numerous clinical studies have been conducted to reduce visceral fat in people living with HIV.
AOD-9604 was studied in preclinical models and in selected human studies, but the range of clinical evidence is much smaller.
In experimental studies, the effects of AOD-9604 on lipid metabolism, bone tissue and cartilage were analyzed, among other things.
The results of such studies do not, however, indicate proven effectiveness in the treatment of obesity, joint diseases, or other conditions.
AOD-9604 does not have FDA approval as a weight-loss drug.
It also cannot be concluded from the limited data that it is safer than tesamorelin, especially with regard to long-term use.
Differences in regulatory status and the quality of clinical evidence are more important than the popularity of both substances in informal applications.
Conclusions
Tesamorelin is a synthetic analog of GHRH with a well-described mechanism of action on the growth hormone axis and IGF-1.
The strongest clinical evidence concerns the reduction in the amount of visceral adipose tissue in adult HIV-infected individuals with lipodystrophy.
The studies also indicate changes in liver fat content, selected lipid parameters, immunological markers, and some body composition indicators.
Data regarding cognitive functions, mitochondria and cardiovascular risk are more limited and do not automatically allow for the extension of clinical indications.
Safety issues also remain important, especially regarding IGF-1, the glucose metabolism, and contraindications related to specific diseases and clinical conditions.
The final interpretation of the results requires taking into account the type of study, the size of the population, the length of observation, and whether actual health outcomes were assessed or only intermediate indicators.
Disclaimer
The article is purely educational and informational in nature. It presents the mechanism of action of tesamorelin, the results of scientific research, and selected regulatory information.
It is not medical advice, a dosing instruction, a reconstitution, an injection, or a recommendation to use tesamorelin on its own or in combination with other substances.
Information about clinical trials does not automatically apply to products sold as laboratory reagents. The legal status and approved indications depend on the country and the specific registered medicinal product.
Decisions regarding diagnosis and treatment should be made by qualified medical personnel based on the current product documentation and individual clinical assessment.
References
- LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Tesamorelin. [Updated 2018 Oct 20]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548730/
- Traynor, K. (2010). FDA approves tesamorelin for HIV-associated lipodystrophy. American Journal of Health-System Pharmacy, 67(24), 2082-2082. doi:10.2146/news100082 https://pismin.com/10.2146/news100082
- PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for , Tesamorelin; [cited 2025 April 19]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Tesamorelin
- Fourman LT, Billingsley JM, Agyapong G, Ho Sui SJ, Feldpausch MN, Purdy J, Zheng I, Pan CS, Corey KE, Torriani M, Kleiner DE, Hadigan CM, Stanley TL, Chung RT, Grinspoon SK. Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD. JCI Insight. 2020 Aug 20; 5 (16): e140134. doi: 10.1172/jci.insight.140134. PMID: 32701508; PMCID: PMC7455119. https://pmc.ncbi.nlm.nih.gov/articles/PMC7455119/
- Fourman, L.T., Czerwonka, N., Feldpausch, M.N., Weiss, J., Mamputu, J.C., Falutz, J., Morin, J., Marsolais, C., Stanley, T.L., and Grinspoon, S.K., 2017. visceral fat reduction using tesamorelin is associated with improved liver enzymes in HIV. Aids, 31(16), pp.2253-2259. https://journals.lww.com/aidsonline/abstract/2017/10230/visceral_fat_reduction_with_tesamorelin_is.10.aspx
- Stanley TL, Fourman LT, Feldpausch MN, et al. Effect of tesamorelin on non-alcoholic steatohepatitis in HIV-positive patients: a randomised, double-blind, multicentre study. Lancet HIV. 2019;6(12):e821-e830. doi:10.1016/S2352-3018(19)30338-8 https://pubmed.ncbi.nlm.nih.gov/31611038/
- Stanley TL, Feldpausch MN, Oh J, et al. Effects of tesamorelin on visceral adipose tissue and hepatic fat in HIV-infected patients with abdominal fat accumulation: a randomised clinical trial. JAMA. 2014;312(4):380-389. doi:10.1001/jama.2014.8334 https://pubmed.ncbi.nlm.nih.gov/25038357/
- Falutz J, Potvin D, Mamputu JC, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with safety extension. J Acquir Immune Defic Syndr. 2010;53(3):311-322. doi:10.1097/QAI.0b013e3181cbdaff
- Falutz J, Mamputu JC, Potvin D, et al. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analogue, in human immunodeficiency virus-infected patients with excess abdominal fat: pooled analysis of two multicentre, double-blind, placebo-controlled phase 3 studies with safety data. J Clin Endocrinol Metab. 2010;95(9):4291-4304. doi:10.1210/jc.2010-0490
- Mangili A, Falutz J, Mamputu JC, Stepanians M, Hayward B. Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat. PLoS One. 2015;10(10):e0140358. Published 2015 Oct 12. doi:10.1371/journal.pone.0140358 https://pubmed.ncbi.nlm.nih.gov/26457580/
- Falutz J, Allas S, Mamputu JC, et al. Long-term safety and effect of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation. AIDS. 2008;22(14):1719-1728. doi:10.1097/QAD.0b013e32830a5058 https://pubmed.ncbi.nlm.nih.gov/18690162/
- Mateo MG, Gutiérrez MDM, Domingo P. Tesamorelin in the treatment of excess abdominal fat in HIV-1-infected patients with lipodystrophy. Expert Rev Endocrinol Metab. 2011;6(1):21-30. doi:10.1586/eem.10.83
- Falutz J, Allas S, Blot K, et al. Metabolic effects of growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357(23):2359-2370. doi:10.1056/NEJMoa072375 https://pubmed.ncbi.nlm.nih.gov/18057338/
- Rahman, F., McLaughlin, T., Mesquita, P., Morin, J., Potvin, D., De Chantal, M. and Aberg, J.A., 2023. The effect of tesamorelin in HIV-infected individuals with and without dorsal-neck fat: A post hoc phase III double-blind placebo-controlled analysis. Journal of Clinical and Translational Science, 7(1), p.e40. https://www.cambridge.org/core/journals/journal-of-clinical-and-translational-science/article/effect-of-tesamorelin-in-people-with-hiv-with-and-without-dorsocervical-fat-post-hoc-analysis-of-phase-iii-double-blind-placebo-control-trial/A85B89546C8B7C2B04307E4BB8B69270
- Falutz J, Allas S, Kotler D, et al. A placebo-controlled dose-ranging study of growth hormone-releasing factor in HIV-infected patients with abdominal fat accumulation. AIDS. 2005;19(12):1279-1287. doi:10.1097/01.aids.0000180099.35146.30 https://pubmed.ncbi.nlm.nih.gov/16052083/
- Adrian S, Scherzinger A, Sanyal A, et al. The growth hormone-releasing hormone analogue, Tesamorelin, reduces body fat and increases muscle area in adults with HIV. J Frailty Aging. 2019;8(3):154-159. doi:10.14283/jfa.2018.45 https://pubmed.ncbi.nlm.nih.gov/31237318/
- Makimura H, Murphy CA, Feldpausch MN, Grinspoon SK. Effects of tesamorelin on phosphocreatine recovery in obese subjects with reduced GH. J Clin Endocrinol Metab. 2014;99(1):338-343. doi:10.1210/jc.2013-3436 https://pubmed.ncbi.nlm.nih.gov/24178787/
- Stanley TL, Falutz J, Marsolais C, et al. Reduction in visceral obesity is associated with improved metabolic profile in HIV-infected patients receiving tesamorelin. Clin Infect Dis. 2012;54(11):1642-1651. doi:10.1093/cid/cis251 https://pubmed.ncbi.nlm.nih.gov/22495074/
- Stanley TL, Fourman LT, Wong LP, et al. Growth hormone-releasing hormone reduces circulating markers of immune activation in parallel with effects on hepatic immune pathways in subjects with HIV infection and non-alcoholic steatohepatitis. Clin Infect Dis. 2021;73(4):621-630. doi:10.1093/cid/ciab019 https://pubmed.ncbi.nlm.nih.gov/33852720/
- Makimura H, Feldpausch MN, Rope AM, et al. Metabolic effects of growth hormone-releasing factor in obese subjects with reduced growth hormone secretion: a randomised controlled trial. J Clin Endocrinol Metab. 2012;97(12):4769-4779. doi:10.1210/jc.2012-2794 https://pubmed.ncbi.nlm.nih.gov/23015655/
- Stanley TL, Falutz J, Mamputu JC, Soulban G, Potvin D, Grinspoon SK. Effects of tesamorelin on inflammatory markers in HIV patients with excess abdominal fat: association with visceral fat reduction. AIDS. 2011;25(10):1281-1288. doi:10.1097/QAD.0b013e328347f3f1 https://pubmed.ncbi.nlm.nih.gov/21516030/
- Grinspoon, S.K., Fourman, L., Stanley, T., McGary, C., Benkeser, D. and Cash, R.B., 2025, February. P-433. impact of Tesamorelin on Cardiovascular Disease Risk Prediction Scores in Phase 3 Studies Treatment Arms: subanalysis. In Open Forum Infectious Diseases (Vol. 12, No. Supplement_1, pp. ofae631-633). US: Oxford University Press. https://academic.oup.com/ofid/article/12/Supplement_1/ofae631.633/7988201
- Russo SC, Ockene MW, Arpante AK, et al. Efficacy and safety of tesamorelin in people with HIV taking integrase inhibitors. AIDS. 2024;38(12):1758-1764. doi:10.1097/QAD.0000000000003965 https://pubmed.ncbi.nlm.nih.gov/38905488/
- Baker LD, Barsness SM, Borson S, et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. Arch Neurol. 2012;69(11):1420-1429. doi:10.1001/archneurol.2012.1970 https://pubmed.ncbi.nlm.nih.gov/22869065/
- Friedman SD, Baker LD, Borson S, et al. Effects of growth hormone-releasing hormone on brain γ-aminobutyric acid levels in mild cognitive impairment and healthy aging. JAMA Neurol. 2013;70(7):883-890. doi:10.1001/jamaneurol.2013.1425 https://pubmed.ncbi.nlm.nih.gov/23689947/
- Ellis RJ, Vaida F, Hu K, et al. Effects of tesamorelin on neurocognitive impairment in HIV-infected abdominal obese subjects. J Infect Dis. Published online 15 January 2025. doi:10.1093/infdis/jiaf012 https://pubmed.ncbi.nlm.nih.gov/39813152/#
- González-Sales M, Barrière O, Tremblay PO, et al. Population pharmacokinetic analysis of tesamorelin in HIV-infected patients and healthy subjects. Clin Pharmacokinet. 2015;54(3):285-294. doi:10.1007/s40262-014-0202-x https://pubmed.ncbi.nlm.nih.gov/25358450/