TESAMORELIN (GHRH)

Mechanism of Action
Tesamorelin is a synthetic analogue of human growth hormone–releasing hormone (GHRH). It consists of the 44 amino acids of endogenous GHRH, modified at the N-terminal end with a trans-3-hexenoic acid group to increase resistance to enzymatic degradation. By binding to GHRH receptors in the anterior pituitary, it stimulates the synthesis and secretion of growth hormone (GH), which in turn raises peripheral levels of insulin-like growth factor-1 (IGF-1).
The increased availability of GH and IGF-1 triggers anabolic and lipolytic effects. Tesamorelin reduces visceral fat mass primarily by promoting lipolysis (breakdown of triglycerides) in deep abdominal adipose tissue, accompanied by reductions in circulating triglyceride levels. This selective mechanism explains its ability to decrease intra-abdominal fat associated with metabolic risk, while having less effect on peripheral subcutaneous fat.
 
Known or Proposed Clinical/Therapeutic Uses
Tesamorelin is approved for the reduction of visceral abdominal fat in adults with HIV-associated lipodystrophy receiving antiretroviral therapy. It is the only medication authorized for this indication (marketed as Egrifta) and is not indicated for general obesity or cosmetic weight loss in non-HIV populations. In patients with HIV and central fat accumulation, tesamorelin has been shown to improve body contour by reducing visceral adipose tissue without significantly affecting subcutaneous fat, while also contributing to improvements in metabolic parameters (e.g., triglyceride levels) and body image perception.
Outside the HIV setting, its potential has been investigated in other conditions characterized by excess visceral fat, such as non-alcoholic fatty liver disease, due to its lipolytic effects and IGF-1 elevation; however, these uses remain experimental. It has also been explored in studies of healthy aging because of its anabolic effects (improvements in lean mass), though its primary and approved use remains HIV-associated lipodystrophy.
 
Side Effects or Associated Risks
Clinical trials indicate that tesamorelin is generally well tolerated. The most common adverse effects are injection-site reactions (redness, itching, pain, bruising, occasional swelling) and mild musculoskeletal symptoms such as limb pain, myalgias, or transient arthralgias. Due to increased IGF-1 levels, fluid retention with peripheral edema may occur, sometimes accompanied by joint discomfort or nerve compression symptoms such as numbness and tingling in the hands or wrists (carpal tunnel–like symptoms).
Some patients have reported nausea, vomiting, heartburn, or night sweats, although these are less common. An important consideration is glucose metabolism: tesamorelin may reduce insulin sensitivity and has the potential to raise blood glucose levels, with a risk of inducing or worsening type 2 diabetes; therefore, glucose monitoring is recommended during treatment. (However, in clinical trials involving patients with HIV, no significant differences in average glycemic parameters were observed between tesamorelin and placebo, suggesting a metabolically safe profile in that population.)
Tesamorelin is teratogenic and contraindicated during pregnancy (category X) and in women who may become pregnant. It is also contraindicated in individuals with active disorders of the hypothalamic–pituitary axis (e.g., pituitary tumors) or a history of active malignancy, as elevated IGF-1 could stimulate malignant cell proliferation. Rarely, severe hypersensitivity reactions have been reported; if symptoms such as generalized urticaria, facial edema, difficulty breathing, or tachycardia occur after injection, treatment should be discontinued and medical attention sought immediately.