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GHRH Analogue · 44 AA FDA Approved 2010 (Egrifta)

Tesamorelin

EGRIFTA · EGRIFTA WR · TH9507 · Trans-3-Hexenoyl GHRH

"The most clinically proven GHRH analogue for visceral fat. FDA approved with two Phase III RCTs behind it. The DPP-4 resistant modification makes it more durable than natural GHRH — and the fat loss data is unusually specific: visceral fat only, not subcutaneous."

Type
44 amino acid GHRH analogue
Structure
Trans-3-hexenoyl N-terminus modification
Status
UK: prescription only medicine · WADA: prohibited at all times · US FDA: approved 2010 as EGRIFTA for HIV lipodystrophy
VAT reduction
15–20% (visceral fat) over 26 weeks
Protocol summary
FDA dose
2 mg SubQ daily
Site
Abdomen, rotate
Time to effect
12–26 weeks · VAT returns on stop
FDA-labelled
2 mg SubQ daily · abdomen rotation · continuous use
VAT loss reverses on discontinuation
How we read the evidence
FDA-approved · large Phase 3 evidence base · clear continuous-use protocol with reversible effects on stopping
Animal evidence

GHRH analog mechanism is well-characterised. Tesamorelin acts on pituitary somatotroph cells to stimulate endogenous GH release, with greater enzymatic stability than native GHRH due to the trans-3-hexenoyl modification at the N-terminus. Preclinical work supported the human trials but is not the primary evidence base — the human trial data is.

Human trials (substantial — Phase 3 approved)

Two pivotal Phase 3 RCTs (LIPO-010 and CTR-1011) randomised HIV-infected patients with central fat accumulation 2:1 to tesamorelin 2 mg/day SubQ vs placebo for 26 weeks. Both showed statistically significant reduction in visceral adipose tissue (VAT) by CT measurement, with effects maintained at 52 weeks in the extension phases. Tesamorelin did not significantly affect subcutaneous fat. Treatment-emergent serious adverse events occurred in fewer than 4% of patients during 26-week treatment. Discontinuation results in VAT reaccumulating — the effect is treatment-dependent, not durable.

Clinical practice (FDA-approved)

FDA-approved as Egrifta (2010) and Egrifta SV, with the more concentrated F8 formulation Egrifta WR approved March 2025 (1.28 mg/day equivalent). UK is not a primary market — sourcing is via specialist clinics or off-label peptide channels. Off-label use for non-HIV visceral fat reduction is now established in TRT and longevity-focused clinics, typically at the same 2 mg/day dose. Beyond HIV-lipodystrophy, ongoing trials are evaluating tesamorelin in NAFLD (non-alcoholic fatty liver disease) — promising data on liver fat reduction.

Community use

Most off-label users follow the FDA dose (2 mg SubQ once daily, abdomen, before bed). Some run 5-days-on/2-days-off purely to manage cost and reduce injection-site reactions; the mechanism doesn't require cycling for tachyphylaxis (unlike GHRPs), so the off-days are practical rather than pharmacological. Effective doses below 2 mg are not well-established — the trial data is at 2 mg, and lower doses likely don't deliver comparable VAT reduction.

Convergence

Tesamorelin is the most-evidenced peptide in this category — FDA-approved with multiple Phase 3 trials demonstrating 15–20% VAT reduction at 26 weeks, with effects maintained out to 52 weeks. Standard protocol is 2 mg SubQ daily, run continuously for as long as the visceral fat reduction is wanted. Effects on visceral fat are real, dose-dependent, and reversible — discontinuation causes VAT to reaccumulate. Side effects are typically mild (injection-site reactions, mild fluid retention, modest IGF-1 elevation). Cycling 5-on/2-off is for practical reasons; this is not a peptide that downregulates with continuous use.

Origin & Background

The DPP-4 resistant GHRH

Tesamorelin is a 44 amino acid synthetic analogue of human GHRH, developed by Theratechnologies and approved by the FDA in 2010 as EGRIFTA — the first and only approved treatment for HIV-associated lipodystrophy (excess abdominal fat caused by antiretroviral therapy). A new weekly formulation, EGRIFTA WR, received FDA approval in March 2025.

The key structural innovation is the addition of a trans-3-hexenoic acid group to the N-terminus of the GHRH molecule. This modification protects the peptide from degradation by dipeptidyl peptidase 4 (DPP-4) — the enzyme that rapidly breaks down natural GHRH in the bloodstream. The result is a more durable, more potent GHRH signal than the natural molecule can sustain.

Two pivotal Phase III randomised controlled trials involving 740 HIV patients demonstrated tesamorelin reduced visceral adipose tissue (VAT) by 15–20% over 26 weeks — a selective effect on deep abdominal fat rather than subcutaneous fat. This selectivity is clinically significant because visceral fat is the metabolically dangerous depot associated with cardiovascular disease, insulin resistance, and inflammation.

Key advantage over sermorelin: Tesamorelin is 44 amino acids (the full active length of GHRH) vs sermorelin's 29 amino acids. The DPP-4 resistance makes it more stable and potent in vivo. It has superior Phase III RCT evidence for visceral fat specifically — a more targeted body composition effect than the broader anti-ageing claims of sermorelin.

Science & Mechanism

Visceral fat — targeted lipolysis

Mechanism of Action

1
DPP-4 resistance: The trans-3-hexenoyl N-terminal modification blocks DPP-4 cleavage — the major enzyme that degrades GHRH in plasma. This extends the effective half-life well beyond natural GHRH, allowing sustained pituitary stimulation from a once-daily injection.
2
Pituitary GHRHR binding: Tesamorelin binds GHRH receptors on pituitary somatotrophs with similar affinity to endogenous GHRH, stimulating pulsatile GH release while preserving somatostatin feedback regulation.
3
Selective visceral lipolysis: Elevated GH drives lipolysis preferentially in visceral adipose tissue over subcutaneous fat — the mechanism is not fully elucidated but visceral adipocytes have higher GH receptor density and greater sensitivity to GH-driven lipolysis.
4
IGF-1 and metabolic effects: GH elevation drives hepatic IGF-1 production, improving lean mass, lipid profiles (reduced triglycerides, improved HDL) and potentially insulin sensitivity — though tesamorelin can also increase insulin resistance acutely.
5
Emerging NAFLD application: A 2023 clinical trial in HIV patients with non-alcoholic fatty liver disease showed tesamorelin reduced liver fat content and prevented fibrosis progression — an emerging application beyond lipodystrophy.
Benefits & Evidence

What the data shows

🔥
Visceral fat reduction — selective
Phase III RCTs (n=740 HIV patients) showed 15–20% VAT reduction over 26 weeks. Effect is specific to visceral fat — subcutaneous fat is largely unaffected. This selectivity makes it uniquely suited to addressing metabolic syndrome and cardiovascular risk driven by visceral adiposity.
● Strong — two Phase III RCTs · FDA approved
💉
Lipid profile improvement
Phase III trials showed significant reductions in triglycerides and improvements in HDL cholesterol alongside VAT reduction. The combination of visceral fat loss and lipid improvement addresses key cardiovascular risk factors.
● Strong — Phase III data
🫀
NAFLD / liver fat reduction
2023 clinical trial in HIV patients with NAFLD: tesamorelin reduced liver fat content and prevented hepatic inflammation and fibrosis progression. A Phase II trial in non-HIV NAFLD patients is ongoing. Emerging but potentially significant application.
● Emerging — Phase II data, HIV population
💪
Lean mass and body composition
As a GHRH analogue driving GH and IGF-1, tesamorelin produces modest lean mass gains alongside fat loss — though this is secondary to the visceral fat effect. Body composition improvements are consistent across trials.
● Moderate — secondary endpoint in trials
Things to know

Risks & considerations

⚠️
Best-characterised GHRH analogue safety profile. Tesamorelin has the most comprehensive safety database of any GHRH analogue — 740 patients in Phase III trials. It retains the class risks of GH axis stimulation (water retention, insulin resistance, IGF-1 elevation) but these are well-characterised and manageable with monitoring.
Mild
Injection site reactions — erythema, pruritus, pain. Common, self-limiting. EGRIFTA WR's lower injection volume reduces this significantly.
Moderate
Water retention and joint pain — arthralgia and peripheral oedema occur in 10–18% of users. Dose-dependent, usually manageable with dose reduction.
Moderate
Insulin resistance / glucose elevation — GH acutely impairs insulin sensitivity. Phase III data showed increased risk of pre-diabetes in some patients. Monitor fasting glucose and HbA1c throughout.
Moderate
Elevated IGF-1 above normal range — occurs in a proportion of patients. Keep IGF-1 within age-appropriate reference ranges. Reduce dose if IGF-1 exceeds upper limit of normal.
Serious
Anti-tesamorelin antibodies — develop in 56% of patients at 26 weeks. Cross-reactivity with endogenous GHRH observed in 60% of antibody-positive patients. Clinical significance is unclear — efficacy was maintained — but represents an unknown long-term risk.
Serious
Contraindicated in active malignancy — GH stimulation is contraindicated with any active cancer. Hydrocephaly in rodent offspring — avoid in pregnancy entirely.

⚠ Key Warnings

Effects reverse on cessation — tesamorelin is maintenance therapy. VAT returns to near-baseline within months of stopping. This must be factored into any long-term decision.
WADA prohibited at all times for competitive athletes.
Monitor IGF-1, fasting glucose, HbA1c every 3 months. Antibody development is common — clinical implications are still being studied.
Compounded tesamorelin quality varies significantly. The pharmaceutical product (EGRIFTA WR) offers the highest assurance but at significantly higher cost.