Tesamorelin

Tesamorelin (development code TH9507) is the best-documented GHRH analog: a trans-3-hexenoyl residue on the first amino acid shields the otherwise native GHRH sequence from the enzyme DPP-IV, which quickly dismantles unmodified GHRH 1-44.

What the clinical data show:

• In the phase 3 trial of 412 HIV patients on antiretroviral therapy, visceral adipose tissue fell by 15.2% after 26 weeks of daily dosing while it grew by 5.0% on placebo; triglycerides improved.
• In the extension to 52 weeks the reduction (-18%) held, and visceral fat returned after the compound was stopped.
• Abdominal subcutaneous fat was largely untouched; in a smaller randomized trial (50 participants, six months) liver fat also decreased modestly.
• IGF-1 rose clearly: by 81% on average in phase 3, and in 13 healthy men by 181 µg/l within two weeks, while fasting glucose and insulin-stimulated glucose uptake stayed flat.

The route of action runs through GHRH receptors of the anterior pituitary; GH output stays pulsatile and the IGF-1 brake keeps working, unlike with growth hormone given directly. On pharmacokinetics, the US label reports a mean elimination half-life of 26 minutes in healthy volunteers and 38 minutes in HIV patients once daily subcutaneous dosing had run for two weeks; newer formulations are quoted at 8 to 11 minutes following a single injection. Originally developed for age-related declines in GH secretion, the compound earned its 2010 approval through HIV lipodystrophy: the first published HIV study dates from 2005, phase 3 followed in 2007.

Tolerability in the phase 3 trials was good overall; the data cover 806 HIV patients and durations up to 52 weeks.

• Most common adverse reactions per the label: muscle and joint pain, pain in the arms or legs, fluid retention with swelling, plus redness and itching where the injection went in. Tingling or numbness in the hands belongs to the same group; mostly transient or resolving after discontinuation.
• IGF-1 outside the normal range: after 26 weeks, 47% of treated patients were more than two standard deviations above the age-adjusted mean and 36% more than three. Whether persistently high IGF-1 promotes tumours is not known.
• Glucose tolerance: an HbA1c of 6.5% or higher appeared after 26 weeks in 5% versus 1% on placebo. A slight rise in fasting glucose at two weeks was no longer significant at six months; in healthy men, clamp-measured insulin sensitivity did not change.
• Hypersensitivity in 4%: itching, skin redness, flushing, hives or rash.
• Beyond 52 weeks, robust data are lacking.

This summary is no substitute for medical advice.

• Metabolic effects of a growth hormone-releasing factor in patients with HIV - phase 3 trial in 412 patients over 26 weeks.
• Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial - randomized trial in 50 participants, including liver fat.
• Effects of a growth hormone-releasing hormone analog on endogenous GH pulsatility and insulin sensitivity in healthy men - 13 healthy men, two weeks, GH pulsatility and insulin sensitivity.