There are a wide array of methods and medications that target weight loss, but one has emerged specifically for human immunodeficiency virus (HIV)-infected patients. Tesamorelin is a man-made analogue of growth hormone releasing hormone (GHRH), a hormone critical to regulating growth hormone (GH) in the body. Tesamorelin is FDA-approved for the treatment of visceral adiposity in HIV. This article will explore its effects in reducing fat1.
Tesamorelin has been in development and studied in clinical trials since June of 2005. Tesamorelin for injection, sold under the brand name Egrifta, is the marketed form of tesamorelin. In 2010, the FDA approved Egrifta for the treatment of excess visceral fat (belly fat) in HIV patients with lipodystrophy2. Lipodystrophy refers to a rare condition in which an individual both loses and gains fat in different parts of the body. With this condition, patients may also experience metabolic abnormalities, including dyslipidemia and cardiovascular disease. These symptoms can cause body dysmorphia and lessened quality of life in affected individuals3.
Since its development and approval in lipodystrophy, tesamorelin has been studied for several other indications in clinical trials. These indications include obesity, insulin resistance, and nonalcoholic fatty liver. One study at Massachusetts General Hospital (MGH) is currently evaluating tesamorelin for the treatment of nonalcoholic fatty liver disease (NAFLD). NAFLD is a common condition in obese patients, and investigators hypothesize that tesamorelin may reduce liver fat and improve liver scarring and inflammation in this disease4. However, results are not yet available.
Tesamorelin consists of 44 amino acids and is a man-made analogue of growth hormone-releasing factor (GRF). When a drug is an analogue, it means that it has a very similar chemical structure to the natural substance. Therefore, it acts similarly to the natural substance in the body. Tesamorelin mimics GRF’s mechanism, activating the production and release of human growth hormone (hGH). From there, hGH binds receptors on several types of cells, including adipocytes (fat cells). Binding to these receptors initiates several metabolic pathways, including lipolysis, which is the breakdown of fat4,5. Growth hormone can also bind hepatocytes, which in turn synthesizes insulin like growth factor1 (IGF-1). IGF-1 regulates several of growth hormone’s effects, including fat breakdown and glucose5.
As aforementioned, researchers are evaluating tesamorelin for several conditions, including NAFLD, insulin resistance, and obesity. Although tesamorelin has been studied in conditions associated with excess fat, it is only FDA-approved to treat excess fat in HIV patients. Likewise, healthcare providers can prescribe it for this reason. It is not currently indicated for weight loss management6.
The approval of tesamorelin was based on two clinical trials of similar study design. The studies were placebo-controlled, phase 3 trials that evaluated the safety of efficacy of tesamorelin in HIV-infected patients over the course of six months. These patients had to have a certain level of fat accumulation in their abdominal area, as evidenced by their waste circumference and waste to hip ratio.
Subjects on tesamorelin had significant reductions in visceral adipose tissue (VAT). Additionally, tesamelorin was associated with reductions in triglycerides and cholesterol. Tesamelorin also improved participants’ body image. These results were maintained for up to 52 weeks, representing its efficacy in fat loss in HIV-infected patients7.
The FDA approved tesamorelin in 2010 for the treatment of excess visceral fat in HIV-infected individuals. As aforementioned, the FDA’s approval of tesamorelin was based on two phase three placebo-controlled studies. The studies evaluated 816 HIV-positive patients throughout the course of 58 weeks. Each of these trials showed that tesmorelin induced statistically significant reductions in visceral adipose tissue and waist circumference2.
Common side effects of tesamorelin include leg, arm, and muscle pain. Additionally, because tesamorelin is given via injection, it can cause injection site reactions. Symptoms of this include redness, swelling, pain, irritation, itching, or rash. More serious side effects of tesamorelin include:
Egrifta is provided as vials, which contain two milligrams (mg) total of drug. To administer Egrifta, the drug is mixed with a diluent. Afterwards, the dose is 1.4 mg, or 0.35 mL of the solution. Egrifta is administered subcutaneously every day into the abdomen. Patients should rotate injection sites in the abdomen to avoid irritation and skin damage6.
Overall, tesamorelin is a safe and efficacious agent for the treatment of excess fat in HIV-infected patients. It has demonstrated statistically significant improvements in fat content and quality of life in well-controlled trials in those affected with HIV. Common side effects include pain and injection site reactions. It has also been studied in other conditions, such as NAFLD. However, it is not approved for use in patients that are not HIV-positive.
