Tesamorelin and Visceral Fat: What the 26-Week Trial Found

In a 26-week trial that compared tesamorelin with placebo in 412 patients with HIV who had an accumulation of abdominal fat, the measure of visceral adipose tissue decreased by 15.2% in the tesamorelin group and increased by 5.0% in the placebo group. Those figures come from the abstract on PubMed: Falutz et al. 2007, New England Journal of Medicine. The trial's primary end point was the percent change from baseline in visceral adipose tissue as shown on computed tomography.

Tesamorelin is a human growth hormone-releasing factor analog produced synthetically, according to the FDA prescribing information for tesamorelin for injection (brand name Egrifta SV). The label says tesamorelin stimulates growth hormone secretion and subsequently increases IGF-1 and IGFBP-3 levels. It lists one indication: the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy. MedlinePlus: Tesamorelin Injection describes lipodystrophy as increased body fat in certain areas of the body, and says tesamorelin injection is not used to help with weight loss.

What did the 26-week trial measure, and what changed?

Patients in the trial were randomly assigned to a daily subcutaneous injection of tesamorelin or placebo for 26 weeks, the abstract says, and 86% of them were men. Its secondary end points included triglyceride levels, the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol, the level of insulin-like growth factor I (IGF-I) and self-assessed body image.

The label reports two multicenter, randomized, double-blind, placebo-controlled studies, which it calls Study 1 and Study 2. Its Study 1 is printed with the ClinicalTrials.gov number NCT 00123253 and randomized 412 patients. The abstract gives the same registration number, NCT00123253, and the same count of 412 patients, so the two documents report one trial. The label's Study 1 percentages differ from the abstract's, and the table prints both sets.

Study 1 and Study 2 are separate trials, each with its own registration number and its own participants. This guide prints their figures side by side, as the label does, and does not rank or pool them. The label counts 273 patients in the tesamorelin group and 137 in the placebo group of Study 1, and 270 and 126 in Study 2. Its mean treatment difference in visceral adipose tissue is -31 cm² in Study 1 and -21 cm² in Study 2.

In the abstract, levels of total cholesterol and HDL cholesterol also improved significantly in the tesamorelin group. The label states that the product is not indicated for weight loss management as it has a weight neutral effect. This site's Portion Distortion quizzes compare today's food portions with the portions available 20 years ago, and their introduction says that with the growth in portions have come increases in waistlines and body weight.

How is visceral fat linked to metabolic risk?

A Framingham Heart Study analysis measured abdominal fat by multidetector computed tomography in 3,001 participants who were free of clinical cardiovascular disease. The abstract, on PubMed: Fox et al. 2007, Circulation, separates visceral adipose tissue (VAT) from subcutaneous abdominal adipose tissue (SAT).

Both compartments were significantly associated with blood pressure, fasting plasma glucose, triglycerides and high-density lipoprotein cholesterol. Both were also associated with increased odds of hypertension, impaired fasting glucose, diabetes mellitus and metabolic syndrome. In women, the odds ratio of metabolic syndrome per 1-standard deviation increase was 4.7 for VAT and 3.0 for SAT; in men the figures were 4.2 and 2.5.

After adjustment for body mass index and waist circumference, VAT but not SAT contributed significantly to risk factor variation, the abstract reports. Its authors write that the findings are consistent with the hypothesized role of visceral fat as a unique, pathogenic fat depot. The tesamorelin trial abstract adds that visceral adipose tissue accumulates during antiretroviral therapy in many patients with HIV, a process it says is associated with an increased cardiovascular risk.

Among this site's archived publications for health professionals, The Practical Guide calls waist circumference the most practical tool a clinician can use to evaluate a patient's abdominal fat. It says men who have waist circumferences greater than 40 inches, and women who have waist circumferences greater than 35 inches, are at higher risk of diabetes, dyslipidemia, hypertension, and cardiovascular disease because of excess abdominal fat.

That page carries this site's note: "Reproduced as archived reference, not current guidance." This site's BMI page prints an archived BMI and waist table that pairs each BMI category with waist circumference.

What happened to visceral fat after the injections stopped?

Each of the label's two studies had a 26-week Extension Phase covering weeks 26 to 52. Patients who had completed 26 weeks of tesamorelin were re-randomized to tesamorelin or placebo. The label gives the purpose in these words: "to assess maintenance of VAT reduction and to gather long-term safety data."

In both studies, the rows for patients switched to placebo show a positive change in visceral adipose tissue between weeks 26 and 52: +25 cm² in Study 1 and +24 cm² in Study 2. The label's mean treatment difference for this phase is -22 cm² in Study 1 and -35 cm² in Study 2. Study 1 and Study 2 are separate trials, and this guide does not rank or pool their figures.

What did the liver-fat trial find?

A randomised, double-blind, multicentre trial enrolled 61 people with HIV whose hepatic fat fraction was 5% or more by proton magnetic resonance spectroscopy. Thirty received tesamorelin and 30 received placebo for 12 months, and the primary endpoint was the change in hepatic fat fraction between baseline and 12 months. The abstract is on PubMed: Stanley et al. 2019, Lancet HIV.

Patients receiving tesamorelin had a greater reduction in hepatic fat fraction than patients receiving placebo. The abstract gives an absolute effect size of -4.1%, corresponding to a -37% relative reduction from baseline. After 12 months, 35% of those receiving tesamorelin and 4% of those receiving placebo had a hepatic fat fraction of less than 5%.

Changes in fasting glucose and glycated haemoglobin were not different between the groups at 12 months. The authors' interpretation is that tesamorelin might be beneficial in people with HIV and non-alcoholic fatty liver disease, and that further studies are needed to determine its long-term effects on liver histology.

What side effects and monitoring does the label describe?

The most commonly reported adverse reactions on the label, at more than 5%, are arthralgia, injection site erythema, injection site pruritus, pain in extremity, peripheral edema and myalgia. The incidence of injection site reactions was 25% in treated patients and 14% in placebo-treated patients during the first 26 weeks of the clinical trials. The trial abstract says adverse events did not differ significantly between the two groups, but more patients in the tesamorelin group withdrew because of an adverse event.

Hypersensitivity reactions occurred in 4% of treated patients in clinical trials and included pruritus, erythema, flushing, urticaria and rash. The label's instruction to prescribers for suspected reactions reads: "advise patients to seek prompt medical attention and immediately discontinue treatment." Its patient section names hives, swelling of your face or throat, and shortness of breath or trouble breathing among the symptoms of a serious allergic reaction, and says to "get emergency medical help right away."

The MedlinePlus page has a separate section on overdose. That section says to immediately call emergency services at 911 if the person has collapsed, had a seizure, has trouble breathing, or can't be awakened.

On blood sugar, the label says treatment can result in glucose intolerance. Patients receiving the drug had an increased risk of developing diabetes compared with placebo (5% vs. 1%), with a hazard ratio of 3.3. The label tells prescribers to evaluate glucose status before treatment begins and to monitor all treated patients periodically. The 26-week trial abstract reports that no significant differences were observed in glycemic measures.

The label says the effects of prolonged elevations in IGF-1 levels are unknown, and it directs prescribers to monitor IGF-1 levels during therapy. Among patients treated for 26 weeks, 47% had IGF-1 levels greater than 2 standard deviation scores and 36% had scores above 3. MedlinePlus tells patients that their doctor will order certain lab tests before and during treatment.

The label lists four contraindications. They are disruption of the hypothalamic-pituitary axis due to hypophysectomy, hypopituitarism, pituitary tumor/surgery, head irradiation or head trauma; active malignancy; known hypersensitivity to tesamorelin or the excipients; and pregnancy. Fluid retention may also occur during therapy, the label says, with adverse reactions such as edema, arthralgia and carpal tunnel syndrome.

This guide is general education. Whether a prescription medicine suits one person is a question for that person's own health care provider.

What has not been established?

The label states that the long-term cardiovascular safety of the product has not been established. It also states that there are no data to support improved compliance with anti-retroviral therapies in HIV-positive patients taking it.

Safety and effectiveness in pediatric patients have not been established, the label says, and there is no information on use in patients greater than 65 years of age. It adds that no formal metabolism studies have been performed in humans, and that life-time carcinogenicity studies in rodents have not been conducted with tesamorelin acetate. The label copy cited in this guide is marked "Revised: 02/2024." More pages are listed on the healthy weight topic page.