Tesamorelin is the benchmark for every growth hormone secretagogue sold without approval. It is FDA-approved, backed by two phase 3 trials in 806 patients, and it reduces visceral fat by about 15% vs placebo in adults with HIV and lipodystrophy. It also raises IGF-1, requires glucose monitoring, and its effect disappears when treatment stops.
Key points
- Tesamorelin has been FDA-approved since 2010 to reduce excess abdominal fat in adults with HIV and lipodystrophy [8][9].
- In two phase 3 trials with 806 patients, it was associated with a reduction in visceral fat, a 15.4% effect vs placebo at 26 weeks [3].
- In a 61-patient trial in HIV with fatty liver, a 37% relative reduction in liver fat vs placebo was observed at 12 months [6].
- The label requires glucose and IGF-1 monitoring. In the trials, 36% had IGF-1 above 3 standard deviations at 26 weeks [8].
- When treatment stopped, visceral fat reaccumulated [2].
US status (October 2026): FDA-approved as Egrifta and regulated as a biologic since March 23, 2020, so compounded tesamorelin has no 503A or 503B pathway. MDside uses the approved product only, for its approved use. See the tesamorelin status page.
Tesamorelin is a GH-axis peptide with marketing approval
Tesamorelin is a stabilized analog of human growth hormone-releasing hormone, GHRH(1-44), given subcutaneously once a day [3][7]. It does not supply GH from outside. It stimulates the pituitary to release its own, and IGF-1 rises with it [8]. The FDA approved it in 2010 [9], and the current label indicates it for “the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy” [8].
That approval sets it apart from the secretagogues sold without approval, such as CJC-1295, ipamorelin or MK-677, discussed in CJC-1295, ipamorelin and MK-677: the GH and IGF-1 debate. Tesamorelin offers something those compounds lack: large, placebo-controlled trials reviewed by a regulator [3][9]. Approval of the branded drug does not extend to compounded versions. The status page above explains why the 2020 biologics transition closed that door.
The phase 3 trials reduced visceral fat
The first trial, published in NEJM in 2007, randomized 412 patients with HIV and abdominal fat accumulation to tesamorelin 2 mg daily or placebo for 26 weeks. Visceral fat measured by CT fell 15.2% with tesamorelin and rose 5.0% with placebo. Triglycerides fell 50 mg/dL vs a 9 mg/dL rise, and IGF-1 rose 81.0% vs a 5.0% fall (P < 0.001 for all comparisons). There were no significant differences in glycemic measures or in adverse events, although more patients in the active arm withdrew because of an adverse event [1].
The pooled analysis of the two phase 3 trials included 806 patients randomized 2:1. At 26 weeks, visceral fat fell 15.4% more than with placebo, with no significant change in abdominal subcutaneous fat (P = 0.08). Triglycerides fell, with a 12.3% treatment effect, body image improved, and mean IGF-1 rose 108 ng/mL vs a 7 ng/mL fall with placebo [3]. In a post hoc analysis, patients with at least an 8% visceral reduction had, compared with those who did not reach it, greater improvement in triglycerides and adiponectin and smaller changes in glucose [4].
- 806: patients in the two phase 3 trials [3]
- 15.4%: visceral fat reduction vs placebo at 26 weeks [3]
- 37%: relative reduction in liver fat at 12 months in HIV with fatty liver [6]
Liver fat is the most promising finding
In a 50-patient HIV trial published in JAMA in 2014, six months of tesamorelin were associated with reductions in visceral fat (a 42 cm² effect; P = 0.005) and in liver fat, with a net reduction of 2.9% in lipid-to-water percentage (P = 0.003). The authors described it as a preliminary study, with modest reductions in liver fat [5].
The multicenter Lancet HIV trial (2019) was designed specifically for non-alcoholic fatty liver disease in 61 people with HIV. At 12 months, hepatic fat fraction fell 4.1 points more than with placebo, a 37% relative reduction (p = 0.016). Of treated patients, 35% ended below 5% liver fat, vs 4% with placebo. Fasting glucose and HbA1c did not differ between groups at 12 months [6].
One trial outside HIV tested cognition
The main trial outside the approved indication randomized 152 adults aged 55 to 87, healthy or with mild cognitive impairment, to tesamorelin 1 mg/day or placebo for 20 weeks. It was associated with a favorable effect on cognition (P = 0.03), mainly on executive function (P = 0.005), with a 117% rise in IGF-1 that stayed within the physiological range and a 7.4% reduction in percent body fat [7].
It is a single 20-week trial, and the authors themselves called for longer studies. Mild adverse events were reported by 68% of the active group vs 36% with placebo, and fasting insulin rose 35% in participants with cognitive impairment [7].
Glucose and IGF-1 need monitoring
In the phase 3 trials, glucose changes were not clinically meaningful at 26 or 52 weeks [3]. The detail matters. In the JAMA trial, fasting glucose rose 7 mg/dL more than with placebo at 2 weeks, a difference that was no longer significant at 6 months [5]. The label reports HbA1c of 6.5% or higher in 5% of treated patients vs 1% with placebo at week 26, with a diabetes hazard odds ratio of 3.3, and asks for glucose evaluation before and during treatment [8].
IGF-1 follows a similar pattern. At 26 weeks, 47% of patients had IGF-1 above 2 standard deviation scores and 36% above 3. The label warns that the effects of prolonged elevation are unknown and recommends considering discontinuation if IGF-1 stays high (for example, above 3 standard deviation scores), particularly if the response is not robust [8].
| Monitor | When | Label threshold or finding [8] |
|---|---|---|
| Glucose | Before and during treatment | HbA1c 6.5% or higher in 5% vs 1% on placebo at week 26 |
| IGF-1 | During treatment | Consider stopping if it stays high, for example above 3 SDS |
The effect stops when the drug stops
In the extension phase of the first trial, the visceral fat reduction was sustained at 18% at 52 weeks while patients stayed on treatment. Those switched to placebo regained it: “Upon discontinuation of tesamorelin, VAT reaccumulated.” The authors concluded that the effects do not last beyond treatment [2]. In the pooled analysis, the group that continued tesamorelin maintained its reductions in visceral fat, waist and triglycerides at 52 weeks [3].
The label sets clear limits
- Narrow indication. Approval covers excess abdominal fat in HIV with lipodystrophy. The label states it is not indicated for weight loss, because its effect on weight is neutral, and that long-term cardiovascular safety has not been established [8].
- Contraindications. Active malignancy, disruption of the hypothalamic-pituitary axis, pregnancy and known hypersensitivity [8].
- Local reactions and fluid retention. Injection-site reactions occurred in 25% of treated patients vs 14% with placebo in the first 26 weeks. Edema, arthralgia and carpal tunnel syndrome may also occur [8].
- Europe did not approve it. The EMA application was withdrawn in 2012. The committee had provisionally concluded it could not be approved: it doubted that the fat reduction translated into clinical benefit and was concerned about the IGF-1 rise in a considerable number of patients [10].
Tesamorelin is the benchmark for the class
Tesamorelin shows that stimulating GHRH in humans produces measurable effects: less visceral fat [1][3], less liver fat [5][6] and a cognitive signal in a controlled trial [7]. It also shows the cost of the mechanism, documented in a label: higher IGF-1, glucose monitoring and loss of effect on discontinuation [2][8]. Measure any promise made for an unapproved secretagogue against that record. If you run a peptide program, the approved product and its label are the only defensible starting point, and the 503A vs 503B sourcing guide explains why a pharmacy cannot fill the gap with a compounded version.
References
- Falutz J, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357(23):2359-70. PMID 18057338. Link
- Falutz J, et al. Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation. AIDS. 2008;22(14):1719-28. PMID 18690162. Link
- Falutz J, et al. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. 2010;95(9):4291-304. PMID 20554713. Link
- Stanley TL, et al. Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clin Infect Dis. 2012;54(11):1642-51. PMID 22495074. Link
- Stanley TL, et al. 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):380-9. PMID 25038357. Link
- Stanley TL, et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV. 2019;6(12):e821-e830. PMID 31611038. Link
- Baker LD, 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):1420-9. PMID 22869065. Link
- Theratechnologies Inc. EGRIFTA WR (tesamorelin) prescribing information, revised 03/2025. DailyMed, U.S. National Library of Medicine. Link
- U.S. Food and Drug Administration. EGRIFTA (tesamorelin for injection) prescribing information, BLA 022505. Initial U.S. approval: 2010. Link
- European Medicines Agency. Egrifta: withdrawal of the marketing authorisation application. 2012. Link
This is general information, not medical or legal advice. Rules vary by state and change. Confirm your own facts with counsel.