Tesamorelin

Tesamorelin is a synthetic 44-amino-acid analog of human growth hormone-releasing hormone (GHRH), the hypothalamic peptide that signals the pituitary to release growth hormone. It keeps the full human GHRH(1-44) sequence with a C-terminal amide and adds a trans-3-hexenoyl group to the N-terminal tyrosine. In preclinical work that change made the peptide resistant to dipeptidyl aminopeptidase-IV and slowed its breakdown in rat, dog and human plasma (Ferdinandi et al., 2007). It was developed under the code TH9507.

It is not that drug product, it is not intended for that indication or any clinical use, and it is not for use in people.

Published work on tesamorelin falls into six areas. Each summary below states the model used. Human studies used the pharmaceutical product in clinical settings and describe that product, not the research material sold here.

Design and preclinical pharmacology

Non-clinical studies compared TH9507 with native hGRF(1-44)-NH2. The hexenoyl group resisted dipeptidyl aminopeptidase-IV and slowed in vitro degradation in plasma. Daily repeat studies raised plasma growth hormone and IGF-1 in pigs, rats and dogs, and the apparent elimination half-life in dogs ranged from 21 to 45 minutes. In studies of up to four months, the more pronounced reversible findings in dogs were attributed to sustained supraphysiological growth hormone and IGF-1 (Ferdinandi et al., 2007).

Growth hormone secretion physiology

In 13 healthy men studied over two weeks, tesamorelin increased mean overnight growth hormone, growth hormone pulse area and basal secretion, and raised IGF-1, while insulin-stimulated glucose uptake measured by clamp did not change significantly (Stanley et al., 2011).

Visceral adipose tissue in clinical trials

Two Phase 3, placebo-controlled trials enrolled adults with HIV and excess abdominal fat and measured visceral adipose tissue by CT. The first (412 participants, 26 weeks) reported a 15.2% decrease with tesamorelin against a 5.0% increase with placebo (Falutz et al., 2007). A pooled analysis of both trials (806 participants) reported a placebo-adjusted reduction of about 15% at 26 weeks, maintained at 52 weeks in participants who continued (Falutz et al., 2010). A later review noted that visceral fat reaccumulated after discontinuation (Dhillon, 2011).

Liver fat

A 6-month randomized trial in 50 adults with HIV and abdominal fat accumulation reported reductions in visceral fat and modest reductions in liver fat, with a transient rise in fasting glucose at 2 weeks (Stanley et al., 2014). A 12-month multicentre trial in 61 people with HIV and non-alcoholic fatty liver disease reported an absolute reduction in hepatic fat fraction of 4.1 percentage points versus placebo (Stanley et al., 2019).

Cognition in older adults

A 20-week randomized, double-blind, placebo-controlled trial enrolled 152 adults aged 55 to 87, 66 of them with mild cognitive impairment. Investigators reported a significant effect on a composite cognitive score, driven mainly by executive-function tests, along with higher IGF-1 and lower percent body fat. Mild adverse events were reported by 68% of the active group and 36% of the placebo group (Baker et al., 2012).

Analytical detection and metabolism

One study incubated sermorelin, tesamorelin, CJC-1295 and CJC-1295 with drug affinity complex in vitro, identified and synthesized 19 major metabolites as reference materials, and built an LC-MS/MS method with detection limits generally at or below 1 ng/mL in urine (Memdouh et al., 2021). Immunoaffinity purification with high-resolution mass spectrometry has also detected tesamorelin in plasma, with a lower limit of detection under 50 pg/mL (Knoop et al., 2016).