Tesamorelin — Canada Research Brief

Mechanism

Tesamorelin binds the GHRH receptor on somatotroph cells of the anterior pituitary, triggering pulsatile release of endogenous growth hormone (GH). Because it acts through the native GHRH axis, GH release remains subject to somatostatin-mediated negative feedback — an important distinction from exogenous recombinant GH, where the feedback loop is bypassed.

The N-terminal trans-3-hexenoyl modification blocks DPP-4 cleavage, the main metabolic route that limits the clinical usefulness of unmodified sermorelin. Subcutaneous bioavailability is modest (~4%), and the elimination half-life is approximately 26–38 minutes after a single dose.

Clinical evidence

Falutz et al. (NEJM 2007) reported the pivotal phase-3 trial in HIV- associated lipodystrophy: tesamorelin 2 mg subcutaneously daily reduced visceral adipose tissue by approximately 15% at 26 weeks versus placebo, with sustained IGF-1 elevation and a tolerable safety profile.

Baker et al. (Archives of Neurology 2012) investigated tesamorelin in older adults with mild cognitive impairment and healthy controls, finding improvement on executive-function measures over 20 weeks — the strongest trial-level evidence for cognitive effects of GHRH analogues in an ageing population.

Storage

Store lyophilised tesamorelin at −20°C protected from light. Once reconstituted, it should be used within 2–4 weeks when refrigerated at 2–8°C.