Tesamorelin: Approved Use, Side Effects, and Evidence

Tesamorelin is a synthetic analog of human growth hormone-releasing hormone (GHRH, also called GRF). It keeps the full 44 amino acid sequence and adds a hexenoyl group to the first amino acid. FDA first approved it in 2010 under the brand Egrifta.

Its approved use is narrow: the reduction of excess abdominal fat in HIV-infected adults with lipodystrophy. The label lists four limitations of use. Long-term cardiovascular safety has not been established. Prescribers should weigh continuing treatment in people whose visceral fat has not fallen. It is not indicated for weight loss management because its effect on weight is neutral. There are no data that it improves adherence to antiretroviral therapy.

Tesamorelin does not supply growth hormone. It binds pituitary GHRH receptors and stimulates the body to make and release its own growth hormone in pulses, which in turn raises IGF-1. Growth hormone has fat-releasing effects, and this action is the proposed basis for the drop in visceral and liver fat seen in trials. This mechanism is described in human studies and in the label.

Two phase 3 randomized, placebo-controlled trials in adults with HIV and excess abdominal fat, pooled with extension data, showed reduced visceral fat compared with placebo. Triglycerides fell and IGF-1 rose. The reduction was maintained through 52 weeks in people who stayed on treatment, while abdominal fat under the skin did not change significantly.

A post hoc analysis found that people whose visceral fat fell the most also had better triglyceride and glucose measures. That is an association, not proof of a broader benefit. A separate, smaller 12-month randomized trial in people with HIV and fatty liver disease showed a larger drop in liver fat than placebo.

In the label's extension data, visceral fat rose again within 26 weeks in people switched to placebo. Nearly all controlled evidence comes from people living with HIV. Efficacy and safety in other groups, for general fatty liver disease, body recomposition, longevity, cognition, or recovery, are not established.

The label contraindicates tesamorelin in people with disruption of the hypothalamic-pituitary axis, active malignancy, known hypersensitivity to the drug, and in pregnancy. It has no boxed warning.

Label warnings cover an increased risk of neoplasms, elevated IGF-1 whose long-term effects are unknown, fluid retention including edema, joint pain and carpal tunnel syndrome, glucose intolerance or diabetes, hypersensitivity reactions, skin reactions where the drug is given, and increased mortality in people with acute critical illness. The most common adverse reactions in trials were joint pain, skin redness and itching where the drug is given, pain in the limbs, peripheral swelling, and muscle pain.

Tesamorelin is a prescription medicine in the United States. In Canada, both Egrifta products in the Drug Product Database are listed as cancelled. Any use outside the approved indication is off-label. WADA prohibits tesamorelin in and out of competition as a GHRH analogue.