Tesamorelin
Tesamorelin is a synthetic analog of human growth hormone releasing hormone (GHRH 1-44) carrying a trans-3-hexenoyl group on the N-terminal tyrosine. That single modification is the reason the compound exists: unmodified GHRH is cleaved within minutes by dipeptidyl peptidase-4, and the hexenoyl group blocks that cleavage without changing how the molecule binds the GHRH receptor on pituitary somatotrophs. The result is a peptide that still produces pulsatile, physiologic growth hormone release rather than the flat exogenous GH level you get from injecting growth hormone itself.
- class
- synthetic GHRH (1-44) analog, trans-3-hexenoyl modified
- route
- subcutaneous, abdomen, sites rotated daily
- plasma half-life
- about 26 minutes in healthy subjects, about 38 minutes in HIV-infected subjects
- typical dose
- 2 mg once daily (1.28 mg in the newer room-temperature formulation)
- approval status
- FDA approved 2010 for HIV-associated lipodystrophy, the only GH-axis peptide here with an approval
- storage
- lyophilized refrigerated 2–8°C; reconstituted, use immediately per label, 28-day max in research handling
Tesamorelin Reconstitution & Dosage Protocol
weekly dose · reduces side effects| Phase | Window | Weekly dose | Draw (U-100, 2mL BAC) | Note |
|---|---|---|---|---|
| Tolerance start | Days 1–7 | 1.00 mg | 20 units· 0.20 mL | Half dose to check tolerance. At 5 mg/mL (10 mg vial in 2 mL BAC water) 1 mg is 0.2 mL, which is 20 units on a U-100 syringe. Arthralgia, peripheral edema, and injection site reactions are the three most common complaints in the trials and they tend to appear in the first two weeks, so a lower opening week makes them easier to attribute |
| Standard daily | Weeks 1–26 | 2.00 mg | 40 units· 0.40 mL | 2 mg once daily subcutaneously into the abdomen, rotating the site each day. At 5 mg/mL this is 0.4 mL, which is 40 units. This is the exact dose and duration used in both phase 3 trials. Most self-directed users inject at bedtime on an empty stomach because insulin blunts GH release, though the label itself sets no timing or fasting requirement |
| Primary checkpoint | Week 26 | 2.00 mg | 40 units· 0.40 mL | This is where the pivotal data ends and judgment starts. In the NEJM trial visceral adipose tissue fell roughly 15 percent at 26 weeks against a small gain on placebo. Assess with waist circumference or imaging plus fasting glucose, HbA1c, and IGF-1, not by how you feel. Non-responders at 26 weeks are unlikely to convert with more time |
| Extended use | Weeks 27–52 | 2.00 mg | 40 units· 0.40 mL | The 52-week extension showed the visceral fat reduction was maintained only in subjects who kept dosing. Continued use is the label pattern for an approved indication. IGF-1 and glucose tolerance should be rechecked here, since sustained GH elevation is the mechanism and also the source of the metabolic risk |
| Discontinuation | After stopping | 0.00 mg | 0 units· 0.00 mL | Visceral fat returns after withdrawal. Subjects re-randomized to placebo in the extension regained what they had lost. There is no taper protocol and no rebound beyond that regain, but nobody should start expecting a durable one-time result: this is maintenance therapy in the way it was actually studied |
What is Tesamorelin?
Tesamorelin is a synthetic analog of human growth hormone releasing hormone (GHRH 1-44) carrying a trans-3-hexenoyl group on the N-terminal tyrosine. That single modification is the reason the compound exists: unmodified GHRH is cleaved within minutes by dipeptidyl peptidase-4, and the hexenoyl group blocks that cleavage without changing how the molecule binds the GHRH receptor on pituitary somatotrophs. The result is a peptide that still produces pulsatile, physiologic growth hormone release rather than the flat exogenous GH level you get from injecting growth hormone itself.
It is the only peptide on this site with a full FDA approval. Marketed as Egrifta, it was approved in November 2010 for reducing excess abdominal fat in HIV-infected patients with lipodystrophy, and the formulation has since been revised twice (Egrifta SV, then a room-temperature-stable version dosed at 1.28 mg daily). That approval matters for how the evidence should be read: unlike most research peptides, tesamorelin has phase 3 trials with imaging endpoints, a published safety database, and a label with contraindications, rather than animal data and forum consensus.
The pivotal evidence comes from two 26-week randomized placebo-controlled trials in HIV patients with abdominal fat accumulation. In the 2007 NEJM trial, 2 mg daily reduced visceral adipose tissue by roughly 15 percent while placebo subjects gained slightly, with improvements in triglycerides and the cholesterol ratio, and IGF-1 rose substantially as expected. Crucially, subcutaneous fat and lean mass were largely preserved: the compound moved visceral fat specifically, which is the metabolically relevant depot. The 52-week extension showed the effect held only while dosing continued.
A second research thread, led largely by Steven Grinspoon's group, extended tesamorelin into liver fat. A 2014 JAMA trial reported reduced hepatic fat fraction alongside the visceral fat effect, and a 2019 Lancet HIV trial in HIV-associated non-alcoholic fatty liver disease found tesamorelin reduced liver fat and slowed fibrosis progression over 12 months. This is why the compound appears in metabolic and liver discussions well outside its approved lipodystrophy indication, though all of that work was still done in people living with HIV.
The risk profile follows directly from the mechanism. Raising GH raises IGF-1 and can worsen glucose tolerance, so fasting glucose and HbA1c belong in any monitoring plan, and the label carries contraindications for active malignancy, disrupted hypothalamic-pituitary axis (hypophysectomy, pituitary tumor, head irradiation), and pregnancy. The common adverse effects across the trials were arthralgia, myalgia, peripheral edema, paresthesia, and injection site reactions. Tesamorelin is also prohibited by WADA as a growth hormone releasing factor.