Compound reference
Tesamorelin
Also known as Egrifta, Egrifta SV, Egrifta WR
Tesamorelin (Egrifta) is the GHRH analogue that succeeded — an FDA-approved prescription drug for reducing excess visceral fat in HIV-associated lipodystrophy, backed by solid randomized-trial and meta-analytic evidence. Its label is explicit that it is not a general weight-loss drug.
- CAS
- 218949-48-5
- Formula
- C₂₂₁H₃₆₆N₇₂O₆₇S
- Molar mass
- ≈5135.9 g/mol
- Sequence
- Human GRF(1-44) with an N-terminal trans-3-hexenoyl group for stability
- Half-life
- ≈26–38 min (subcutaneous)
FDA-approved prescription medicine for reducing excess abdominal fat in adults with HIV-associated lipodystrophy; not indicated for weight-loss management.
Mode of action
Tesamorelin is a stabilized analogue of growth hormone-releasing factor — the full 44-amino-acid human GRF (i.e. GHRH) sequence with a trans-3-hexenoyl group attached to the N-terminus to resist enzymatic degradation. Like sermorelin it is a GHRH-receptor agonist that stimulates the pituitary to release growth hormone in a physiologic, feedback-regulated way, raising circulating GH and IGF-1. The downstream effect that earned it approval is on body fat: the elevated GH axis drives lipolysis, and clinically this preferentially reduces visceral (intra-abdominal) adipose tissue.
Main intended effect
Reduction of excess visceral abdominal fat — specifically in the setting of HIV-associated lipodystrophy.
Areas of interest
The approved indication is HIV-associated lipodystrophy, where antiretroviral therapy can drive a disfiguring and metabolically harmful accumulation of visceral fat. A second, well-studied strand is liver fat — tesamorelin reduces hepatic steatosis in this population, which has drawn interest in NAFLD/MASLD more broadly. It is important to separate these from how the peptide is marketed in the gray market, where it is sold as a general fat-loss or "anti-aging" GH booster.
Evidence for intended effects
Tesamorelin is the GHRH analogue with the strongest evidence, because it was developed as a real drug. A pivotal phase 3 trial randomized 404 HIV patients with abdominal fat accumulation to tesamorelin or placebo and showed significant visceral-fat reduction, and a second pooled phase 3 analysis linked that VAT reduction to improved metabolic markers. A JAMA randomized trial then showed tesamorelin reduces liver fat as well as visceral fat. A 2026 meta-analysis of five randomized controlled trials quantified the effect — visceral adipose tissue reduced by about 28 cm², trunk fat by about 1.2 kg, and hepatic fat by about 4.3% versus placebo. On this basis the FDA approved Egrifta in 2010.
The crucial qualifier is indication. This evidence is in HIV-associated lipodystrophy; the prescribing information is explicit that tesamorelin is not indicated for general weight management, and the trials were not designed to support anti-aging or athletic use. The benefit also reverses on discontinuation, since it depends on ongoing GH-axis stimulation.
| Strand | What exists | Tier |
|---|---|---|
| HIV lipodystrophy — visceral fat | Multiple phase 3 RCTs + meta-analysis; FDA-approved | Established (approved) |
| Liver fat (in HIV) | Randomized JAMA trial | Strong RCT |
| General weight loss / anti-aging | Not indicated; not studied for this | Not supported |
Studied amounts (literature dosing context)
In the pivotal trials tesamorelin was given at 2 mg subcutaneously once daily; the approved Egrifta SV product is dosed at 1.4 mg subcutaneously once daily. These are the regulated, label-defined clinical figures for the HIV-lipodystrophy indication; this page does not provide dosing guidance for any other use.
Safety and regulatory status
Tesamorelin is an FDA-approved prescription medicine (Egrifta, later Egrifta SV) for reducing excess abdominal fat in HIV-associated lipodystrophy, with a defined safety profile, contraindications (including pregnancy and active malignancy), and monitoring (it raises IGF-1). It is not approved for weight loss or anti-aging, and the gray-market sale of "tesamorelin" for those purposes is off-label, with the usual unverified-identity-and-purity concerns of compounded or research-grade peptide. It belongs to the GHRH-analogue family alongside sermorelin and CJC-1295, and is the only member currently holding FDA approval.
Sources
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
Pivotal phase 3 randomized, double-blind, placebo-controlled trial (Falutz et al.) enrolling 404 HIV-infected patients with excess abdominal fat on antiretroviral therapy, randomized 2:1 to tesamorelin 2 mg subcutaneously daily versus placebo for an initial 6-month efficacy phase followed by a 12-month safety extension. The primary endpoint, visceral adipose tissue (VAT), fell 10.9% (-21 cm2) with tesamorelin versus 0.6% (-1 cm2) with placebo (P<0.0001), with concurrent improvement in trunk fat, waist circumference, and waist-hip ratio but no change in limb or abdominal subcutaneous fat. IGF-1 rose significantly (P<0.001) without change in glucose parameters, roughly 18% VAT reduction was sustained over 12 months on continued treatment, and benefits reversed on crossover to placebo. The trial population was predominantly male, and durability beyond the studied window was not established.
Effect of Tesamorelin on Visceral Fat and Liver Fat in HIV-Infected Patients With Abdominal Fat Accumulation: A Randomized Clinical Trial
Single-center double-blind randomized placebo-controlled trial (Stanley et al.) of 50 antiretroviral-treated HIV-infected patients with abdominal fat accumulation, assigning tesamorelin 2 mg subcutaneously daily (n=28) versus placebo (n=22) for 6 months. Tesamorelin reduced VAT by a mean 34 cm2 versus an 8 cm2 placebo increase (treatment effect -42 cm2, P=0.005) and lowered hepatic fat fraction (median -2.0% vs +0.9%; net -2.9%, P=0.003). Fasting glucose rose transiently at 2 weeks and resolved by 6 months, HbA1c showed a modest increase (P=0.03), and AST decreased (P=0.046). The study was small and underpowered for secondary endpoints, included no liver biopsies, was primarily male, and the cohort was not preselected for elevated liver fat.
Reduction in Visceral Adiposity Is Associated With an Improved Metabolic Profile in HIV-Infected Patients Receiving Tesamorelin
Pooled analysis (Stanley, Falutz, et al.) of two phase 3 randomized double-blind placebo-controlled tesamorelin trials, combining 402 tesamorelin-treated and 197 placebo-treated per-protocol subjects given 2 mg subcutaneously daily over 26 weeks with a 26-week extension. Responders (>=8% VAT reduction) reached 69% at 26 weeks and 72% at 52 weeks versus 33% on placebo (P<0.001), with mean VAT loss of -50 cm2 at 26 weeks. VAT reduction tracked with improved triglycerides (responder vs nonresponder triglyceride change -0.6 vs -0.1 mmol/L, P=0.005) and smaller HbA1c rise (0.1% vs 0.3%, P<0.001), and percent VAT change correlated with triglyceride (rho=0.174, P=0.001) and HbA1c (rho=0.206, P<0.001) improvement. Analysis was per-protocol rather than intent-to-treat, used HOMA-IR rather than direct insulin-sensitivity measures, and did not address safety beyond 52 weeks.
Body composition, hepatic fat, metabolic, and safety outcomes of Tesamorelin, a GHRH analogue, in HIV-associated lipodystrophy: A meta-analysis of randomized controlled trials
Meta-analysis (Badran et al.) pooling five randomized controlled trials of tesamorelin versus placebo in adults with HIV-associated lipodystrophy. Tesamorelin reduced visceral adipose tissue by 27.71 cm2 (95% CI -38.37 to -17.06; P<0.001), trunk fat by 1.18 kg (P<0.001), and hepatic fat by 4.28% (P<0.001) while increasing lean body mass by 1.42 kg (P<0.001), with no significant change in subcutaneous adipose tissue or BMI. CD4+ T-cell counts were unchanged and glucose was not meaningfully perturbed; reported adverse events were arthralgia, myalgia, paresthesia, and injection-site erythema, with no serious adverse effects flagged. The pooled estimates summarize trial-level data and do not substitute for individual long-term cardiovascular safety evidence, which remains unestablished per labeling.
Egrifta (tesamorelin acetate) NDA 22-505 FDA Summary Review
FDA Center for Drug Evaluation and Research Division Director Summary Review (Mary H. Parks, M.D.) for NDA 22-505, recommending approval of Egrifta (tesamorelin acetate), a synthetic growth hormone-releasing factor (GHRF/GHRH) analog, for reduction of excess abdominal fat in HIV patients with lipodystrophy. The document describes Egrifta as a 44-amino-acid peptide of human GHRF modified with a hexenoyl moiety at the N-terminus to extend half-life while retaining activity as a hypothalamic peptide stimulating pituitary GH release, supplied as a 1.1 mg lyophilized powder dosed 2 mg subcutaneously once daily. The applicant was Theratechnologies Inc.; the recommended action was approval dated November 5, 2010. This establishes the GHRH-analog regulatory precedent for the approved HIV-lipodystrophy indication.
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022505Orig1s000SumR.pdf
EGRIFTA SV (tesamorelin) for injection, for subcutaneous use — Prescribing Information
FDA prescribing information (DailyMed) for EGRIFTA SV (tesamorelin) by Theratechnologies Inc., indicated for reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy, with initial US approval in 2010. The recommended dose is 1.4 mg (0.35 mL reconstituted) subcutaneously once daily. The label contraindicates use in patients with disruption of the hypothalamic-pituitary axis, active malignancy, hypersensitivity to tesamorelin, or pregnancy, and warns of increased neoplasm risk, elevated IGF-1, fluid retention, glucose intolerance, hypersensitivity reactions, and that long-term cardiovascular safety has not been established. Most common adverse reactions (>5%) include arthralgia, injection-site erythema and pruritus, pain in extremity, peripheral edema, and myalgia. This is the labeling document, not a primary efficacy study; it is not indicated for weight management.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224