Tesamorelin

Tesamorelin is a synthetic analogue of human GHRH(1-44), the hypothalamic hormone that tells the pituitary to release growth hormone [1][9]. Unlike injected growth hormone, it works through the body's own growth hormone release: in healthy men it raised both basal and pulsatile secretion [2].

Visceral fat in HIV. Some people on antiretroviral therapy build up visceral fat. In the first phase 3 trial (412 patients), 26 weeks of 2 mg daily cut visceral fat by 15.2%, while it rose 5.0% on placebo. Triglycerides fell by 50 mg/dL [10]. A second trial of 404 patients reported similar results [9]. Pooled across both trials (806 patients), the treatment effect was −15.4%. Subcutaneous fat barely changed, and body-image scores improved [3]. People who stayed on the drug for 52 weeks kept the loss (about −18%), but visceral fat came back in those switched to placebo [6]. A 2026 meta-analysis of five trials also found more lean mass and a smaller waist, with no change in BMI [11].

Liver fat. In a 50-person trial, 6 months of tesamorelin reduced liver fat as well as visceral fat [4]. In 61 people with HIV and fatty liver disease, 12 months lowered the liver fat fraction by 37% relative to baseline. Liver fat fell below the 5% threshold in 35% on tesamorelin and 4% on placebo [5]. Liver biopsies showed fibrosis progressing in 10.5% on tesamorelin and 37.5% on placebo, but the drug did not reverse existing fibrosis [5].

Cognition. In 152 adults aged 55–87, with or without mild cognitive impairment, 1 mg nightly for 20 weeks improved a combined cognitive score. The effect came mainly from executive function; verbal memory showed only a trend [7]. A 73-person open-label trial in people with HIV and cognitive impairment found no significant difference from standard care over 6 months [8].

Tesamorelin activates the GHRH receptor on the pituitary, which releases growth hormone in its natural pulses. Growth hormone in turn raises IGF-1 from the liver [1][2]. In the phase 3 trials, IGF-1 rose by 81% [10]. In older adults it rose 117% but stayed within the normal range [7]. The fat loss is selective: visceral fat falls while subcutaneous fat barely changes [3].

Across the phase 3 trials tesamorelin was generally well tolerated. Treatment-emergent serious adverse events occurred in under 4% of patients over 26 weeks, and most events were injection-site reactions or known effects of growth hormone, such as joint pain, headache and swelling of the legs [1]. In the first trial, overall adverse events did not differ from placebo, but more people on tesamorelin withdrew because of one [10]. A meta-analysis lists joint pain, muscle pain, tingling and injection-site redness [11]. In older adults, 68% on tesamorelin reported mild adverse events, against 36% on placebo. These were mainly skin reactions and joint pain, with some tingling in the hands and fluid retention [7].

Glucose. Over 26 and 52 weeks, the phase 3 trials found no clinically meaningful change in glucose [3][6]. Fasting glucose did rise at 2 weeks in the liver-fat trial and then settled [4]. In the fatty-liver trial, two people on tesamorelin stopped for worsening high blood sugar, one of whom already had diabetes [5]. Fasting insulin rose 35% in older adults with mild cognitive impairment [7]. In healthy men, insulin sensitivity measured by clamp did not change [2].