Tesamorelin (Egrifta / Egrifta SV)

Tesamorelin is a synthetic analog of endogenous growth hormone-releasing hormone (GHRH) containing all 44 amino acids of native GHRH with a trans-3-hexenoic acid modification at the N-terminal tyrosine. Its CAS number is 218949-48-5, and its molecular weight is 5,135.86 Da. The N-terminal modification is the key innovation. Native GHRH is rapidly degraded by dipeptidyl peptidase-4 (DPP-4) in the bloodstream, giving it a half-life of just a few minutes. The trans-3-hexenoic acid cap protects tesamorelin from this enzymatic cleavage, extending its biological activity while maintaining the same receptor binding affinity as natural GHRH. Tesamorelin was FDA-approved in November 2010 under the brand name Egrifta for reducing excess abdominal fat in HIV-infected patients with lipodystrophy. The approval was based on two Phase 3 trials enrolling 816 patients, which showed 15-18% reduction in visceral adipose tissue at 26 weeks, maintained through 52 weeks of treatment. Tesamorelin reduced visceral fat while preserving subcutaneous fat. That distinction matters because subcutaneous fat is metabolically less harmful. Beyond the FDA indication, a 2019 study published in The Lancet HIV (PMID: 31611038) tested tesamorelin in 61 HIV-infected patients with non-alcoholic fatty liver disease. Over 12 months, tesamorelin reduced liver fat by 37%, with 35% of treated patients achieving normal liver fat levels versus 4% on placebo. The study also showed that tesamorelin prevented progression of hepatic fibrosis. The peptide stimulates pulsatile GH release through the body's natural feedback mechanisms, raising IGF-1 levels by approximately 81% compared to baseline. Unlike direct GH injection, the hypothalamic-pituitary feedback loop remains intact, preventing supraphysiological GH levels. The short half-life (26-38 minutes at steady state) is actually advantageous. It mimics the natural pulsatile pattern of GH release rather than maintaining artificially elevated levels. Tesamorelin is frequently stacked with ipamorelin in anti-aging and body composition protocols. The combination stimulates GH release through two different pathways (GHRH receptor and ghrelin receptor), producing a stronger and more sustained GH pulse than either compound alone. Cycling (60-90 days on, 2-4 weeks off) is typically recommended to prevent receptor desensitization. As an FDA-approved drug, tesamorelin was not placed on the FDA Category 2 restricted list that affected 19 other peptides in late 2023, and it was not affected by the February 2026 HHS reclassification. It remains legally available through both standard prescription and compounding pharmacies. Brand Egrifta costs $3,000-6,000/month without insurance, while compounded versions typically run $150-450/month. Contraindications include active malignancy (GH/IGF-1 can promote tumor growth), pregnancy (Category X), disruption of the hypothalamic-pituitary axis, and known hypersensitivity. The most common side effects are injection site reactions (~25%), arthralgia, and fluid retention. About 4.5-5% of treated patients developed new diabetes versus 1% on placebo, so glucose monitoring is important.