Description
Tesamorelin is a stabilized GHRH analog in which the natural GHRH sequence is modified by a trans-3-hexenoyl group at position 1. This modification makes the compound substantially more resistant to DPP-IV degradation than unmodified GHRH 1-44. According to the US prescribing information (FDA), the mean elimination half-life after 14 days of subcutaneous dosing was 26 minutes in healthy subjects and 38 minutes in HIV patients; for the newer formulations, 8 to 11 minutes after a single dose are given. Tesamorelin has been approved as a medicine in the US since 2010 and was studied in two phase 3 trials with a combined 806 participants.
Tesamorelin (code TH9507) was first developed for age-associated conditions with reduced GH secretion. The trials that led to approval were then run in HIV patients with excess abdominal fat on antiretroviral therapy (first published HIV study in 2005, phase 3 including Falutz et al., NEJM 2007): visceral fat decreased, while abdominal subcutaneous fat stayed largely unchanged.
Mechanistically, tesamorelin acts through GHRH receptors of the anterior pituitary and stimulates endogenous GH secretion. In contrast to exogenous HGH, the natural negative feedback regulation via IGF-1 is preserved, making the compound a more physiologically grounded research tool. IGF-1 rises clearly: by 81% on average in the phase 3 trial and by 181 µg/l in 13 healthy men after 2 weeks of daily dosing.
In the clinical trials, tesamorelin was given subcutaneously once daily. The primary endpoint of the phase 3 trials was the change in visceral fat; IGF-1 was recorded as a secondary endpoint.
Tesamorelin is available in 10-vial packs at 5mg, 10mg and 20mg per vial.
This information is for research and educational purposes only. No medical recommendations.
Risks & Safety
In the phase 3 trials, tesamorelin was generally well tolerated. The safety data come mainly from these trials with a combined 806 HIV patients over up to 52 weeks. According to the US prescribing information, the most common adverse reactions are joint pain, redness and itching at the injection site, pain in the arms or legs, swelling from fluid retention and muscle pain.
Described in studies and the prescribing information:
- Injection site: redness, itching, pain or irritation at the injection site are among the most common adverse reactions.
- GH-typical effects: fluid retention, joint and muscle pain as well as numbness or tingling in the hands (carpal-tunnel-type symptoms). According to the prescribing information, they are usually transient or resolve after stopping.
- IGF-1 above the normal range: after 26 weeks, IGF-1 was more than 2 standard deviations above the age-adjusted mean in 47% of treated patients. In 36% it was more than 3. Whether prolonged elevated IGF-1 affects the development or growth of tumours is unknown according to the prescribing information.
- Glucose metabolism: the US prescribing information warns of glucose intolerance: an HbA1c of 6.5% or more occurred after 26 weeks in 5% on tesamorelin and 1% on placebo. In one trial, fasting blood glucose rose slightly after 2 weeks. The difference was no longer significant after 6 months. In healthy men, insulin sensitivity measured by clamp was unchanged.
- Hypersensitivity: 4% of treated patients had hypersensitivity reactions in the trials, with itching, skin redness, flushing, hives or rash.
- No long-term data: despite clinical studies up to 52 weeks, robust human studies over very long periods for research use do not exist.
This classification does not replace medical advice. Risk and responsibility for any actual use lie entirely with the buyer.
Studies
- Metabolic effects of a growth hormone-releasing factor in patients with HIV - New England Journal of Medicine 2007: Phase 3 trial in 412 HIV patients with abdominal fat accumulation: after 26 weeks of daily dosing, visceral adipose tissue decreased by 15.2% versus a 5.0% increase with placebo, alongside improved triglyceride levels.
- Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation - AIDS 2008: Extension phase over a total of 52 weeks: the reduction in visceral fat (-18%) and triglycerides was sustained with continued dosing, while visceral fat reaccumulated after discontinuation.
- Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data - Journal of Clinical Endocrinology & Metabolism 2010: Pooled analysis of two phase 3 trials with 806 participants: visceral fat decreased by 15.4% versus placebo, abdominal subcutaneous fat was unchanged, IGF-1 rose and glucose parameters showed no clinically meaningful differences.
- Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial - JAMA 2014: Randomized, placebo-controlled trial in 50 participants over 6 months in which liver fat decreased modestly in addition to visceral fat. Fasting glucose was slightly above placebo after 2 weeks but no longer significantly different after 6 months.
- Effects of a growth hormone-releasing hormone analog on endogenous GH pulsatility and insulin sensitivity in healthy men - Journal of Clinical Endocrinology & Metabolism 2011: 13 healthy men, 2 weeks once daily subcutaneously: GH secretion rose in pulses and at baseline, IGF-1 by 181 µg/l, while fasting glucose and insulin-stimulated glucose uptake were unchanged.
