What Is Tesamorelin?

Tesamorelin is a synthetic peptide analog of human growth hormone–releasing hormone (GHRH).
It contains the full 44–amino-acid sequence of GHRH with specific modifications that improve stability and resistance
to enzymatic degradation such as dipeptidyl peptidase-IV
(source).

Mechanism of Action

1. GHRH Receptor Activation

Tesamorelin binds to GHRH receptors in the anterior pituitary, stimulating the pulsatile release of endogenous growth hormone (GH).
This in turn activates hepatic and systemic production of insulin-like growth factor-1 (IGF-1)
(PMC3038486,
NBK548730).

2. Downstream Metabolic Signals

GH and IGF-1 signaling support anabolic processes and stimulate lipolysis in adipose tissue,
while also influencing lipid and glucose metabolism
(NBK539131).

3. Resistance to Degradation

Modifications in tesamorelin’s structure increase its half-life and bioavailability,
allowing for a sustained physiological effect following subcutaneous administration
(PMC3038486).

Scientific Findings (Contextual Research)

Visceral Fat Reduction

In a randomized study, tesamorelin reduced visceral adipose tissue (VAT) by approximately 10.9% at 6 months
and ~18% at 12 months compared with placebo
(PubMed 20101189).

Body Composition & Lipid Profiles

Additional research showed VAT reductions of up to 17.5% at 52 weeks, decreased triglycerides, and improved lipid ratios
(PubMed 20554713).

Hepatic Gene Expression

Tesamorelin modulated liver gene expression in HIV-associated NAFLD,
enhancing oxidative phosphorylation and downregulating inflammatory and proliferative gene sets
(PubMed 32701508).

Metabolic Safety in Diabetes

In type 2 diabetes studies, tesamorelin did not significantly affect glycemic control,
but did modestly reduce total and non-HDL cholesterol
(PubMed 28617838).

Neurocognitive Research (Exploratory)

A phase 2 open-label study in HIV patients with abdominal obesity noted reductions in waist circumference and increased IGF-1,
though cognitive outcomes were not statistically significant
(PubMed 39813152).

Selected PubMed References

• Falutz J et al., 2010 — Visceral fat reduction study
• Falutz J et al., 2010 — Extended 52-week VAT and lipid outcomes
• Fourman LT et al., 2020 — Hepatic gene expression modulation
• Clemmons DR et al., 2017 — Metabolic safety in diabetes
• Ellis RJ et al., 2025 — Exploratory neurocognitive findings