Tesamorelin
Tesamorelin (GHRH Analogue)
Tesamorelin (Egrifta) is the only FDA-approved GHRH analogue, indicated for reduction of excess visceral adipose tissue in HIV-infected adults with lipodystrophy. It consists of the complete 44-amino-acid GHRH sequence with a trans-3-hexenoic acid modification that protects against DPP-IV degradation.
Mechanism of Action
Tesamorelin binds and activates pituitary GHRH receptors with the full-length 44-amino-acid native GHRH sequence, producing more complete pituitary signalling than the 29-amino-acid fragments (sermorelin, CJC-1295). Its lipid modification provides resistance to DPP-IV cleavage, extending the biological activity window.
Visceral fat reduction is mediated through increased pulsatile GH secretion, which drives IGF-1 elevation and subsequent lipolysis in visceral adipocytes — the fat depot most responsive to GH-mediated lipolysis.
Research Evidence
Tesamorelin has the most extensive human clinical trial dataset of any GHRH analogue, accumulated during its FDA approval programme. Effects on visceral adiposity, metabolic parameters, and cognitive function have been studied in multiple populations.
Tesamorelin Reduces Visceral Adiposity in HIV Lipodystrophy (Phase 3)
In two Phase 3 trials (n=816), tesamorelin 2mg/day SC significantly reduced trunk fat by 15–18% vs placebo at 26 weeks, with improvements in triglycerides, HDL, and body image measures.
Typical Research Protocol
This is the FDA-approved dose for lipodystrophy. Off-label research protocols for visceral fat reduction outside HIV contexts use the same dose. IGF-1 monitoring is recommended during long-term use.
Safety Profile
Reported Side Effects
- Arthralgia (joint pain)
- Oedema
- Myalgia
- Injection site redness
- Nausea
- Headache
Contraindications
- Active malignancy
- Pregnancy
- Hypopituitarism
- Disruption of hypothalamic-pituitary axis from prior tumours/surgery/radiation
Common Research Stacks
Frequently Asked Questions
Is tesamorelin only for HIV patients?
FDA approval is specifically for HIV-associated lipodystrophy. Research and clinical use outside this indication is off-label. The mechanism of visceral fat reduction is not HIV-specific — elevated GH/IGF-1 reduces visceral adiposity regardless of HIV status — so tesamorelin is studied and used off-label for other forms of visceral obesity and metabolic syndrome.
How does tesamorelin compare to CJC-1295?
Tesamorelin is the complete 44-amino-acid GHRH sequence versus CJC-1295's 29-amino-acid truncated form. Tesamorelin may produce more complete pituitary GHRH receptor activation. CJC-1295 is more flexible (can be dosed 2–3× daily for multiple pulses). For visceral fat specifically, tesamorelin has direct Phase 3 human evidence that CJC-1295 lacks.
What does tesamorelin do to visceral fat?
In FDA Phase 3 trials, tesamorelin 2mg/day produced 15–18% reduction in trunk fat measured by DEXA at 26 weeks. Effects are mediated through GH-driven lipolysis in visceral adipocytes — the fat depots most responsive to GH action. The reduction includes metabolically dangerous visceral fat (intra-abdominal) more than subcutaneous fat.
Can tesamorelin improve cognitive function?
Several studies have explored tesamorelin's cognitive effects, particularly in older adults. A 20-week RCT found tesamorelin improved executive function and verbal memory versus placebo in non-HIV older adults. The cognitive benefits are thought to be mediated through IGF-1 elevation and its neuroprotective effects in the hippocampus and prefrontal cortex.
How long does the effect of tesamorelin last after stopping?
In HIV lipodystrophy trials, visceral fat rebounded toward baseline within 6–12 months after stopping tesamorelin. This rebound indicates the drug suppresses rather than eliminates the underlying metabolic drivers of visceral fat accumulation. Maintenance dosing is often required for sustained benefit, similar to other chronic disease treatments.
Key Research References
- Falutz J et al. (2010). Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med.
- Stanley TL et al. (2012). Effects of tesamorelin on non-alcoholic fatty liver disease. Clin Gastroenterol Hepatol.
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