Overview

Tesamorelin is a synthetic analog of human growth-hormone-releasing hormone (GHRH), consisting of the full 44-amino-acid GHRH(1-44) sequence with a trans-3-hexenoyl moiety covalently attached to the N-terminal tyrosine. That modification confers resistance to enzymatic degradation — particularly by dipeptidyl-peptidase-IV — and extends functional exposure relative to native GHRH and to the shorter fragment Sermorelin (GHRH 1-29).

Unlike most peptides commonly discussed in research contexts, tesamorelin has a clear regulatory history. It received FDA approval in 2010 (as Egrifta, developed by Theratechnologies) for the reduction of excess visceral adipose tissue in HIV-infected adults with lipodystrophy. It remains the only GHRH analog with an active US approval in that indication as of this writing.

Mechanism (as reported in the literature)

  • GHRH-receptor agonism. Tesamorelin binds the pituitary GHRH receptor and stimulates pulsatile release of endogenous growth hormone.
  • DPP-IV resistance. The trans-3-hexenoyl modification at the N-terminus is reported to slow enzymatic clearance, giving tesamorelin a functionally longer window of receptor engagement than unmodified GHRH.
  • Preserved feedback loops. As with other GHRH agonists, endogenous negative feedback via somatostatin and IGF-1 is described as remaining intact, so GH release retains a pulsatile rather than tonic character.
  • IGF-1 elevation. In the pivotal HIV-lipodystrophy trials, mean IGF-1 rose within the age-adjusted reference range at the 2 mg/day dose.

Research findings

  • Pivotal Phase 3 (Falutz et al., 2007). A 26-week randomised trial in HIV-infected adults with excess abdominal fat reported a mean reduction in visceral adipose tissue of roughly 15–18% at 2 mg/day subcutaneously, with abdominal subcutaneous fat preserved. Triglycerides and the triglyceride/HDL ratio also declined. Published in the New England Journal of Medicine (PMID 18057338).
  • Extension and long-term safety (Falutz et al., 2010). A follow-on study evaluated an additional 26 weeks of exposure and reported that the reduction in visceral adipose tissue was maintained in patients who continued therapy and largely reversed in patients switched to placebo, suggesting the effect is contingent on ongoing administration. Published in JCEM around 2010.
  • Metabolic-profile analyses (Stanley et al., 2011, 2014). Secondary analyses reported associations between the visceral-fat reduction and improvements in triglycerides, adiponectin, and hepatic fat fraction on MRI-based measurements, in HIV-infected populations.
  • NAFLD exploratory work. Later trials evaluated tesamorelin in HIV-infected adults with hepatic steatosis and reported reductions in liver fat fraction relative to placebo (Stanley et al., 2019, Lancet HIV).

Common dosing (from published research protocols)

The pivotal trials used 2 mg subcutaneously once daily, administered in the abdomen. Reported human research doses fall in a narrow window of approximately 1–2 mg daily; the 2 mg dose is the one associated with the approved regimen. These are ranges reported in the clinical literature and are not recommendations.

Reconstitution

A 5 mg vial of tesamorelin acetate reconstituted with 2 mL of bacteriostatic water yields a 2,500 mcg/mL (2.5 mg/mL) solution.

  • 1,000 mcg (1 mg) = 0.4 mL = 40 units on a U-100 insulin syringe
  • 2,000 mcg (2 mg) = 0.8 mL = 80 units

Because the trial dose is at the upper end of typical peptide-research volumes, some references discuss reconstituting a 5 mg vial in 1 mL bacteriostatic water to give a 5,000 mcg/mL solution, halving the injection volume.

Storage

Lyophilised tesamorelin is reported as stable when refrigerated. Once reconstituted, product labelling and research literature describe stability for a limited number of days at 2–8 °C; long-term storage is generally reported to be at freezer temperatures.

  • Sermorelin — the unmodified GHRH(1-29) fragment; tesamorelin can be viewed as a longer, stabilised counterpart.
  • CJC-1295 no DAC — an alternative approach to stabilising the GHRH backbone via amino-acid substitution rather than N-terminal acylation.
  • CJC-1295 DAC — a long-acting, albumin-binding GHRH analog for contrast on pharmacokinetics.
  • Ipamorelin — a selective GH-secretagogue often discussed alongside GHRH analogs.

Common stacks

References

  • Falutz, J., et al. (2007). “Metabolic effects of a growth hormone-releasing factor in patients with HIV.” New England Journal of Medicine, 357(23), 2359–2370. PMID 18057338.
  • Falutz, J., et al. (2010). “Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation.” AIDS, 24(2). (Falutz JCEM/AIDS extension study.)
  • Stanley, T. L., et al. (2011). “Effects of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation.” JAMA, 306(8). PMID 21862744.
  • Stanley, T. L., et al. (2019). “Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial.” Lancet HIV, 6(12).