Tesamorelin

Tesamorelin is a modified growth hormone releasing hormone studied chiefly for the excess visceral fat that can develop in adults living with HIV. Its strongest evidence comes from randomized trials that measured fat around the abdominal organs and followed what happened when treatment continued or stopped. Those trials support its approved use in HIV associated lipodystrophy. Smaller studies also found reductions in liver fat and examined a selected group of adults with abdominal obesity and reduced growth hormone secretion. The results are most useful when the fat compartment, population and formulation remain clear.

Overview

Tesamorelin contains the 44 amino acid sequence of human growth hormone releasing hormone, with a hexenoyl group attached at its beginning. This modification changes the molecule's susceptibility to breakdown while preserving its ability to stimulate the pituitary receptor. Pharmaceutical tesamorelin is supplied as an acetate salt. The current Egrifta WR prescribing information identifies that form and its approved indication.

Molecular profile

Peptide backbone: 44 amino acid human GHRH sequence Source
N terminal modification: Hexenoyl group attached to the N terminal tyrosine Source
Pharmaceutical form: Tesamorelin acetate Source
Molecular formula: C221H366N72O67S · x(C2H4O2), x approximately 7, as stated for the acetate in the label Source
Molecular weight: 5135.9 Da, free base equivalent reported in the label Source

Forms and derivatives

Egrifta WR

Tesamorelin acetate formulation with different strength and preparation requirements from SV. Its current label reports an eleven minute mean peptide elimination half-life and states that WR and SV are not substitutable.

Egrifta SV

A distinct tesamorelin acetate formulation whose label reports an eight minute mean elimination half-life after single subcutaneous administration in healthy subjects.

Earlier Egrifta formulation

The pivotal trials used an earlier formulation. Its label reported repeated administration half-life means of 26 minutes in healthy subjects and 38 minutes in people with HIV, a different exposure context from the current WR and SV estimates.

Egrifta formulations

Egrifta WR and Egrifta SV contain the same active peptide but differ in strength, formulation and preparation requirements. The WR label expressly states that they are not substitutable. The original efficacy trials used an earlier Egrifta formulation; the WR label connects its clinical use to that evidence through comparative systemic exposure. Consequently, a product name and study formulation are necessary parts of interpreting a tesamorelin result.

Uses and research areas

The approved use is reduction of excess abdominal fat in adults with HIV associated lipodystrophy. Lipodystrophy refers to altered body fat distribution, which can combine fat accumulation around the organs with loss of fat elsewhere. CT imaging can separate visceral fat from the subcutaneous fat lying beneath the skin, allowing investigators to determine which compartment changes.

Research has extended to liver fat because fat deposited within the liver can accompany visceral adiposity. Stanley and colleagues (2014) examined both compartments in adults with HIV, and Stanley and colleagues (2019) enrolled people with HIV and established fatty liver. A separate trial by Makimura and colleagues (2012) selected adults with abdominal obesity and reduced stimulated GH secretion. These populations define the questions that the trials can answer.

Mechanism of action

Growth hormone releasing hormone, also called growth hormone releasing factor, normally carries a signal from the hypothalamus to growth hormone (GH) producing cells in the anterior pituitary. Tesamorelin stimulates this receptor, increasing endogenous GH secretion and the downstream insulin-like growth factor 1 (IGF-1). GH acts on adipose tissue, liver and other tissues; IGF-1 mediates part of its effects. This gives the intervention a plausible connection to fat mobilization, tissue growth and glucose regulation. The hormone response also explains why IGF-1 and glucose measurements matter in safety assessment.

Early fragment research helps explain this receptor approach. In five healthy volunteers, Losa and colleagues (1984) found that the 29, 40 and 44 residue releasing hormone preparations all stimulated GH. Tesamorelin's clinical development added a defined modification to the full length hormone and tested the resulting preparation in a specific body composition disorder. Its clinical interpretation depends on those subsequent outcomes.

Pharmacokinetics

Egrifta WR elimination illustrated from its reported mean half-life

Population: Healthy human subjects; sample size not supplied in the labeling section. Administration: Subcutaneous; modeled elimination phase after absorption. Analyte: Plasma tesamorelin represented as modeled normalized C/C0.

Normalized elimination illustration using the eleven minute Egrifta WR mean in healthy subjects after subcutaneous administration. The line begins at 100% and represents the peptide elimination phase. The label supplies no numerical uncertainty for this mean. A constant half-life produces C/C0 = 2^(-t/11), with time in minutes. Absorption and differences between people are outside this illustration; hormone responses have separate time courses.

Theratechnologies Inc. Prescribing information section 12.3, Elimination: single subcutaneous Egrifta WR administration in healthy subjects.

The current labels report a mean elimination half-life of 11 minutes for Egrifta WR and 8 minutes for Egrifta SV, each after a single subcutaneous administration in healthy subjects. These values describe circulating tesamorelin. The older Egrifta label (2019) reported means of 26 and 38 minutes in healthy subjects and people with HIV after repeated administration of the earlier formulation. Formulation, population and sampling context therefore belong beside every quoted half-life.

The illustration uses the WR mean to show an idealized elimination phase beginning at a normalized 100%. It assumes a constant half-life and calculates the fraction remaining as C/C0 = 2^(-t/11), with time in minutes. Absorption, the actual starting concentration and differences between people are outside this calculation. GH secretion and later IGF-1 changes follow their own time courses, so the curve cannot show the duration of the endocrine response or the time required for a change in abdominal fat.

Research findings

Visceral fat in the pivotal HIV trials

Falutz and colleagues (2007) randomized 412 adults with HIV and abdominal fat accumulation to tesamorelin or placebo for 26 weeks. Visceral adipose tissue decreased 15.2% with tesamorelin and increased 5.0% with placebo. IGF-1 increased 81.0% in the active group and declined 5.0% in the placebo group. Overall adverse event frequency did not differ significantly, although more tesamorelin recipients withdrew because of an adverse event. Group glycemic measures were similar during that trial.

Falutz and colleagues (2010) reported a second randomized trial involving 404 participants, followed by a continuation or withdrawal extension. At six months, visceral fat decreased 10.9% with tesamorelin and 0.6% with placebo. Continued exposure was associated with an approximately 18% reduction at 12 months. Participants switched to placebo rapidly lost the earlier reduction. Limb and abdominal subcutaneous fat were unchanged. Together, the two trials establish a reproducible visceral fat effect and show that its maintenance depended on continued treatment.

Liver fat and biopsy findings

The six month trial by Stanley and colleagues (2014) randomized 50 adults with HIV to tesamorelin or placebo; 48 received study drug. Scans measured the area occupied by fat around the abdominal organs. This area fell by 42 cm² more with tesamorelin than with placebo, a treatment difference of −42 cm² with a 95% confidence interval from −71 to −14. The liver lipid-to-water measurement, another way to estimate stored fat, also decreased, with a net difference of −2.9 percentage points. Fasting glucose rose more with tesamorelin at two weeks. At six months, the comparisons of fasting and two hour glucose did not establish a difference between groups.

Stanley and colleagues (2019) compared tesamorelin with placebo in 61 adults with HIV whose liver fat fraction was at least 5%. During the 12 month blinded phase, liver fat fell by 4.1 percentage points more with tesamorelin, an absolute treatment effect of −4.1 percentage points and a corresponding relative reduction of 37%. Liver samples taken before and after treatment suggested that scarring progressed less often with tesamorelin. The comparison did not establish improvement in existing scarring. Nor did it establish improvement in the overall disease activity score, inflammation or ballooning, the swelling of injured liver cells. These findings distinguish reducing stored fat and slowing the development of scarring from reversing established liver injury.

A selected abdominal obesity population

Makimura and colleagues (2012) randomized 60 adults with abdominal obesity and reduced GH secretion for 12 months. HIV and diabetes were excluded. The visceral fat treatment effect was −35 cm², whereas the abdominal subcutaneous fat difference of −10 cm² was not significant and BMI was unchanged. The wall of the carotid artery became thinner, triglycerides fell and C-reactive protein, a marker of inflammation, decreased more with tesamorelin than with placebo. These are risk related measurements; the trial did not measure cardiovascular event prevention. The full report also records two discontinuations for persistently elevated IGF-1.

Laboratory metabolism

Memdouh and colleagues (2021) studied how tesamorelin and three other releasing hormone analogues broke down in laboratory systems. They also added known amounts to urine to test how the peptides and their breakdown products could be detected and distinguished. These analytical experiments provide information about chemical identity and breakdown; the human blood measurements and clinical outcomes above came from separate studies.

Safety and tolerability

Tesamorelin's approved indication does not extend to general weight loss, and long term cardiovascular safety remains unestablished. The current prescribing information identifies active malignancy, pregnancy, disruption of the hypothalamic pituitary axis and hypersensitivity as contraindications. It describes IGF-1 elevation, fluid retention, joint and muscle symptoms, glucose intolerance or diabetes, and local or systemic allergic reactions. A critical illness warning draws on increased mortality reported with pharmacologic GH after surgery, trauma or acute respiratory failure. These concerns follow from both the injected preparation and its endocrine effects.

Over the baseline-to-Week-26 period, the label's combined trial account records new HbA1c values of at least 6.5% in 5% of tesamorelin recipients and 1% of placebo recipients. Thus, unchanged mean glucose in individual trials coexists with an increased diabetes signal in the broader safety analysis. The label also calls for attention to medications whose metabolism may change with GH stimulation and to glucocorticoid replacement. The available evidence supports clinical monitoring within the approved setting; it supplies limited information about prolonged use for other purposes.

What the research means

Tesamorelin has unusually clear clinical evidence within this peptide family: two randomized trials found a selective reduction in visceral fat in adults with HIV, and withdrawal data showed the effect reversing after exposure stopped. The liver studies extend that biological observation to a related fat depot and offer an encouraging fibrosis progression result, while preserving important negative histology findings.

The remaining questions concern patient outcomes and broader applicability. Less visceral or liver fat may be useful, but the trials did not establish fewer heart attacks, liver complications or deaths. The obesity study's endocrine selection and exclusions also matter when considering a wider population. Shared stimulation of GH provides a biological connection to other releasing hormone analogues; each preparation still needs its own clinical evidence.

FAQs

Is tesamorelin approved for weight loss?

Its approved use concerns excess abdominal fat in adults with HIV associated lipodystrophy. The Egrifta WR label states that it is not indicated for weight loss management. The pivotal studies measured visceral fat, and a selected obesity trial found unchanged BMI despite a reduction in that compartment.

Which kind of abdominal fat changed?

Visceral fat surrounds the abdominal organs; subcutaneous fat lies beneath the skin. Falutz and colleagues (2010) found lower visceral fat with no change in limb or abdominal subcutaneous fat. This compartment response explains why a weight change is an incomplete description of the result.

What happened after treatment stopped?

In the withdrawal extension reported by Falutz and colleagues (2010), participants who continued maintained the visceral fat reduction, while those switched to placebo rapidly lost the initial improvement. The effect depended on continued exposure over the follow-up period.

Did tesamorelin reverse liver scarring?

In adults with HIV and fatty liver, samples taken before and after treatment suggested that liver scarring progressed less often with tesamorelin than with placebo. The comparison did not establish improvement in scarring already present, and the overall disease activity score did not improve clearly. Stanley and colleagues (2019) therefore provide evidence about slowing progression, with no established reversal of existing injury.

Why are several half-lives quoted?

Formulation, population and administration history differ. The WR and SV labels report eleven and eight minute means after single subcutaneous administration in healthy subjects; the earlier label reported 26 and 38 minutes after repeated administration in two populations. Peptide elimination also differs from the GH and IGF-1 time courses.

Are Egrifta WR and SV interchangeable?

The WR label states that they are not substitutable. They share the active peptide but differ in formulation strength and preparation requirements. Study exposure must be interpreted with the actual formulation identified.

Sermorelin uses the first 29 residues of the releasing hormone and has a substantial historical childhood growth literature. CJC-1295 with DAC adds an albumin binding unit to a modified fragment and produced prolonged hormone changes in early human studies. Modified GRF(1–29) contains sequence substitutions but lacks that DAC extension. Comparing these compounds is useful for understanding chemical design, exposure and the different outcomes that investigators measured.

References

Falutz J, Allas S, Blot K, Potvin D, Kotler D, Somero M, Berger D, Brown S, Richmond G, Fessel J, Turner R, Grinspoon S. Metabolic effects of a growth hormone-releasing factor in patients with HIV. The New England journal of medicine. 2007;357(23):2359–2370. DOI: 10.1056/NEJMoa072375. PMID: 18057338.
The original randomized HIV trial measured a selective visceral fat reduction and a substantial IGF-1 increase.
Falutz J, Potvin D, Mamputu JC, Assaad H, Zoltowska M, Michaud SE, Berger D, Somero M, Moyle G, Brown S, Martorell C, Turner R, Grinspoon S. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension. Journal of acquired immune deficiency syndromes (1999). 2010;53(3):311–322. DOI: 10.1097/QAI.0b013e3181cbdaff. PMID: 20101189.
The second randomized HIV lipodystrophy trial documented lower visceral fat and loss of the reduction after switching to placebo.
Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, Grinspoon SK. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. 2014;312(4):380–389. DOI: 10.1001/jama.2014.8334. PMID: 25038357.
A six month HIV trial measured reductions in visceral and liver fat and an early fasting glucose rise.
Stanley TL, Fourman LT, Feldpausch MN, Purdy J, Zheng I, Pan CS, Aepfelbacher J, Buckless C, Tsao A, Kellogg A, Branch K, Lee H, Liu CY, Corey KE, Chung RT, Torriani M, Kleiner DE, Hadigan CM, Grinspoon SK. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. The lancet. HIV. 2019;6(12):e821–e830. DOI: 10.1016/S2352-3018(19)30338-8. PMID: 31611038.
A randomized HIV fatty liver trial measured liver fat reduction and less fibrosis progression, with no significant reversal of existing fibrosis.
Makimura H, Feldpausch MN, Rope AM, Hemphill LC, Torriani M, Lee H, Grinspoon SK. Metabolic effects of a growth hormone-releasing factor in obese subjects with reduced growth hormone secretion: a randomized controlled trial. The Journal of clinical endocrinology and metabolism. 2012;97(12):4769–4779. DOI: 10.1210/jc.2012-2794. PMID: 23015655.
A selected obesity trial measured lower visceral fat, with no significant subcutaneous fat difference and unchanged BMI.
Memdouh S, Gavrilović I, Ng K, Cowan D, Abbate V. Advances in the detection of growth hormone releasing hormone synthetic analogs. Drug testing and analysis. 2021;13(11-12):1871–1887. DOI: 10.1002/dta.3183. PMID: 34665524.
The investigators studied peptide breakdown in laboratory systems and added known amounts to urine to test detection methods. They distinguished sermorelin, tesamorelin and CJC-1295 preparations with and without DAC.
Losa M, Schopohl J, Müller OA, von Werder K. Stimulation of growth hormone secretion with human growth hormone releasing factors (GRF1-44, GRF1-40, GRF1-29) in normal subjects. Klinische Wochenschrift. 1984;62(23):1140-1143. DOI: 10.1007/BF01782473. PMID: 6240568.
A healthy volunteer comparison demonstrated acute GH releasing activity of three fragment lengths, including GRF(1-29).
Theratechnologies Inc. Egrifta WR (tesamorelin) prescribing information. DailyMed SPL version 2, effective 29 July 2026; prescribing text revised March 2025.
Current WR labeling identifies the approved HIV lipodystrophy use, formulation distinction and eleven minute mean elimination half-life.
Theratechnologies Inc. Egrifta SV (tesamorelin) prescribing information. DailyMed, accessed 13 October 2026; prescribing information revised February 2024.
SV labeling reports an eight minute mean elimination half-life after single subcutaneous administration in healthy subjects.
Theratechnologies Inc. Egrifta WR prescribing information. FDA approved labeling, March 2025.
Approved labeling supplies contraindications and the combined clinical diabetes safety account.
Theratechnologies Inc. Egrifta prescribing information. FDA approved labeling, 2019.
Earlier labeling reports repeated administration half-life means of 26 and 38 minutes in different populations.

Glossary

GHRH: Growth hormone releasing hormone, a hypothalamic peptide that stimulates GH producing pituitary cells.
IGF-1: Insulin-like growth factor 1, produced in liver and other tissues and mediating part of the GH response.
Pharmacokinetics: The study of how a compound enters, moves through and leaves the body.
Half-life: Time for an assayed concentration to fall by half during a specified disappearance or elimination phase.
Amidation: A chemical modification at the end of a peptide chain, indicated by NH2 in these names.
Visceral adipose tissue: Fat around the abdominal organs, measured separately from fat beneath the skin.
Fibrosis: Accumulation of scar tissue in an organ.
Confidence interval: A statistical range describing uncertainty around an estimated difference.
Lipodystrophy: Altered fat distribution, including regional loss or accumulation.