Tesamorelin HIV Lipodystrophy Trials Review
Tesamorelin is the only FDA-approved drug for reducing excess visceral abdominal fat in adults with HIV-associated lipodystrophy. Sold under the brand name Egrifta, it earned that approval in November 2010 based on two large Phase III trials involving more than 800 patients.
Tesamorelin is the only FDA-approved drug for reducing excess visceral abdominal fat in adults with HIV-associated lipodystrophy. Sold under the brand name Egrifta, it earned that approval in November 2010 based on two large Phase III trials involving more than 800 patients.
But what did those trials actually measure? How strong were the results? And what have follow-up studies revealed about benefits beyond fat reduction?
This article walks through every major clinical trial of tesamorelin in HIV lipodystrophy, from the first Phase II proof-of-concept to the most recent liver fat studies. We'll cover the study designs, the numbers, the limitations, and what the data means for patients and clinicians today.
Table of Contents
- What Is Tesamorelin?
- The Problem It Was Designed to Solve
- Phase II: The Proof-of-Concept (Falutz et al., 2007)
- Pivotal Phase III Trial 1: LIPO-010
- Pivotal Phase III Trial 2: CTR-1011
- Pooled Analysis of Both Phase III Trials
- Extension Phase Results: 52 Weeks of Data
- Beyond Fat: The NAFLD Study (Stanley et al., 2019)
- Safety Profile Across All Trials
- What Happens When You Stop
- How Tesamorelin Compares to Other Approaches
- Summary of Key Trial Data
- FAQ
- The Bottom Line
- References
What Is Tesamorelin?
Tesamorelin is a synthetic 44-amino acid analog of human growth hormone-releasing hormone (GHRH). It differs from natural GHRH by a single modification: a trans-3-hexenoic acid group attached to the N-terminal tyrosine. This small structural change gives tesamorelin greater resistance to enzymatic breakdown, meaning it stays active in the body longer than the hormone it mimics.
Rather than replacing growth hormone directly, tesamorelin stimulates the pituitary gland to produce and release growth hormone in a pulsatile, physiological pattern. That downstream increase in growth hormone and IGF-1 drives the reduction in visceral fat that made the drug clinically useful.
Theratechnologies, a Montreal-based biotech company, developed tesamorelin and brought it through clinical trials under the guidance of Dr. Julian Falutz at McGill University Health Centre.
The Problem It Was Designed to Solve
HIV-associated lipodystrophy is a syndrome that emerged in the late 1990s as antiretroviral therapy (ART) became widespread. Patients on ART began developing abnormal fat distribution: visceral fat accumulated in the abdomen while subcutaneous fat wasted from the face, limbs, and buttocks.
This wasn't just cosmetic. Excess visceral adipose tissue (VAT) in HIV patients is linked to increased cardiovascular risk, insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD). It also carries real psychological consequences -- many patients reported distress over visible body changes that effectively "outed" their HIV status.
Before tesamorelin, there was no approved treatment. Recombinant human growth hormone (rhGH) reduced visceral fat but caused insulin resistance and glucose intolerance. Diet and exercise helped some patients, but VAT often proved stubborn. A targeted approach was needed.
Phase II: The Proof-of-Concept (Falutz et al., 2007)
The first major clinical trial of tesamorelin in HIV lipodystrophy was published in the New England Journal of Medicine in 2007. This study established that the drug could selectively reduce visceral fat without the metabolic problems seen with growth hormone.
Study Design:
- 412 HIV-infected patients with clinical lipodystrophy
- Randomized, double-blind, placebo-controlled
- 2:1 randomization (tesamorelin 2 mg subcutaneous daily vs. placebo)
- 26-week treatment period
- Primary endpoint: percent change in VAT measured by CT scan at L4-L5 level
Key Inclusion Criteria:
| Criterion | Requirement |
|---|---|
| Age | 18-65 years |
| Waist circumference (men) | 95 cm or greater |
| Waist circumference (women) | 94 cm or greater |
| Waist-to-hip ratio (men) | 0.94 or greater |
| Waist-to-hip ratio (women) | 0.88 or greater |
| Fasting blood glucose | Less than 150 mg/dL |
| CD4 count | Greater than 100 cells/mm3 |
| Viral load | Less than 10,000 copies/mL |
| Stable ART | At least 8 weeks |
Results:
Tesamorelin produced a selective loss of approximately 1.0 kg of visceral fat over six months. The effect was specific to the visceral compartment -- subcutaneous fat and limb fat were not significantly affected.
Triglycerides dropped by 50 mg/dL in the tesamorelin group while increasing by 9 mg/dL in the placebo group. The total cholesterol-to-HDL ratio improved significantly. IGF-1 levels rose by 81% (109 ng/mL) in treated patients.
Importantly, glucose and insulin parameters did not worsen -- a meaningful contrast to what had been observed with direct growth hormone administration.
This trial gave the green light for the two pivotal Phase III studies that would form the basis of FDA approval.
Pivotal Phase III Trial 1: LIPO-010
LIPO-010 was the first of two registration trials. It enrolled 412 HIV-infected patients with excess abdominal fat across multiple centers.
Design:
- 26-week main phase followed by 26-week extension
- Randomization: 2:1 (tesamorelin 2 mg SC daily vs. placebo)
- At week 26, tesamorelin patients were re-randomized to continue tesamorelin or switch to placebo
- Placebo patients all switched to tesamorelin for the extension
Primary Endpoint Result (26 Weeks):
VAT decreased significantly more with tesamorelin than placebo. The treatment group showed approximately a 15% reduction in visceral adipose tissue, while the placebo group showed minimal change.
Trunk fat, waist circumference, and waist-to-hip ratio all improved in the tesamorelin arm. Limb fat and abdominal subcutaneous fat did not change significantly -- confirming the drug's selectivity for visceral stores.
Pivotal Phase III Trial 2: CTR-1011
CTR-1011 followed a nearly identical design to LIPO-010, enrolling 404 HIV-infected patients with lipodystrophy.
Design:
- Multicenter, randomized, double-blind, placebo-controlled
- 26-week main phase plus 26-week extension
- 2:1 randomization (tesamorelin vs. placebo)
- Same re-randomization structure in the extension phase
Primary Endpoint Result (26 Weeks):
VAT decreased by 10.9% (approximately 21 cm2) in the tesamorelin group versus 0.6% (approximately 1 cm2) in the placebo group (P < 0.0001).
Additional findings included significant improvements in trunk fat (P < 0.001), waist circumference (P = 0.02), and waist-to-hip ratio (P = 0.001). Limb fat and subcutaneous abdominal fat were unaffected.
Patient-reported body image distress also improved in the tesamorelin arm -- a finding that mattered to patients who experienced real psychological burden from lipodystrophy.
Pooled Analysis of Both Phase III Trials
Falutz and colleagues published a pooled analysis of both Phase III trials in the Journal of Clinical Endocrinology & Metabolism in 2010, combining data from 806 ART-treated HIV patients (543 tesamorelin, 263 placebo).
Results at 26 Weeks:
| Outcome | Tesamorelin | Placebo | P-Value |
|---|---|---|---|
| VAT change (cm2) | -24 +/- 41 | +2 +/- 35 | < 0.001 |
| Treatment effect on VAT | -15.4% | -- | -- |
| Triglycerides | Significant decrease | No change | < 0.001 |
| Total cholesterol/HDL ratio | -0.31 | +0.21 | < 0.001 |
| IGF-1 | Increased ~81% | Decreased ~5% | < 0.001 |
| Glucose parameters | No significant change | -- | NS |
The pooled analysis confirmed the consistency of results across both trials and across geographic sites. It also showed that lipid improvements tracked with the degree of visceral fat reduction -- patients who lost more VAT also saw bigger drops in triglycerides.
Extension Phase Results: 52 Weeks of Data
The extension phases of both trials provided the longest controlled data available at the time of FDA approval. A total of 578 patients continued into the extension.
Key Findings:
Patients who stayed on tesamorelin for the full 52 weeks maintained their visceral fat reduction. In a responder analysis, VAT decreased from 187 cm2 to 137 cm2 by week 26 (approaching normal levels of less than 130 cm2) and reached a mean of 129 cm2 by week 52.
Patients who were switched from tesamorelin to placebo at week 26 saw their visceral fat rebound. Trunk fat increased by approximately 1.1-1.4 kg over the following 26 weeks in these "switch" patients.
Lean body mass remained stable in patients continuing tesamorelin, suggesting the drug did not cause muscle wasting.
IGF-1 levels stayed elevated in patients continuing treatment and returned to baseline in those switched to placebo.
Beyond Fat: The NAFLD Study (Stanley et al., 2019)
One of the most clinically significant post-approval studies examined tesamorelin's effect on liver fat. Published in The Lancet HIV in 2019, this randomized trial addressed a growing concern: NAFLD affects over one-third of people living with HIV and follows a more aggressive course than in the general population, with higher rates of NASH and liver fibrosis.
Study Design:
- 61 men and women with HIV and hepatic fat fraction (HFF) of 5% or greater
- Randomized to tesamorelin 2 mg daily or placebo for 12 months
- Primary endpoint: change in hepatic fat fraction by proton magnetic resonance spectroscopy
- Two academic centers
Results:
Tesamorelin reduced hepatic fat fraction by an absolute 4.1% compared to placebo (P = 0.02), representing a 37% relative reduction.
35% of patients in the tesamorelin group dropped below the 5% hepatic fat threshold (meaning they no longer met criteria for NAFLD) versus just 4% in the placebo group (P = 0.007).
The drug also appeared to prevent fibrosis progression. Among patients with NASH at baseline, those receiving tesamorelin showed favorable shifts in inflammation and fibrosis markers, including reductions in VEGFA and TGFB1 -- proteins involved in tissue scarring and blood vessel growth.
This study positioned tesamorelin as the only agent to date showing efficacy against liver fat specifically in the HIV population.
Safety Profile Across All Trials
Across more than 800 patients in controlled trials lasting up to 52 weeks, tesamorelin showed a manageable safety profile. But the data contains some important nuances.
Common Adverse Events (More Than 5%, Greater Than Placebo):
| Adverse Event | Tesamorelin | Placebo |
|---|---|---|
| Arthralgia (joint pain) | Reported more frequently | Lower rate |
| Injection site erythema | Common | Less common |
| Injection site pruritus | Common | Less common |
| Pain in extremity | Reported | Lower rate |
| Peripheral edema | Reported | Lower rate |
Glucose and Diabetes:
This is the most scrutinized safety signal. Elevated HbA1c (6.5% or greater) developed in 5% of tesamorelin patients versus 1% of placebo patients by week 26. An FDA briefing document reported an odds ratio of 3.3-3.6 for developing diabetes with tesamorelin versus placebo, depending on how baseline cases were handled.
The FDA label warns that tesamorelin can cause glucose intolerance and recommends monitoring glucose before and during treatment.
Immunogenicity:
Anti-tesamorelin IgG antibodies were detected in roughly 50% of patients by 26 weeks. About 60% of those antibodies cross-reacted with endogenous GHRH. However, antibody development did not reduce the drug's efficacy -- patients with and without antibodies had similar VAT reductions.
IGF-1 Elevation:
47% of patients had IGF-1 levels above 2 standard deviations, and 36% exceeded 3 standard deviations by 26 weeks. While this did not produce clinical problems during the trial period, the long-term implications of sustained IGF-1 elevation remain an open question. The FDA required a post-marketing observational study to track cancer risk over 10 years.
What Happens When You Stop
One consistent finding across all tesamorelin trials: the effects are not permanent. When patients stopped taking the drug, visceral fat returned and lipid improvements reversed -- typically within 26 weeks.
This pattern matches the pharmacology. Tesamorelin stimulates endogenous growth hormone release. When you remove the stimulus, growth hormone returns to its prior (often suppressed) level, and the metabolic effects fade.
The extension phase data showed this clearly. Patients switched from tesamorelin to placebo at week 26 experienced VAT rebound, triglyceride increases, and IGF-1 normalization. Patients who continued treatment maintained their gains.
This means tesamorelin, as currently used, requires ongoing administration -- an important consideration given cost and the need for daily subcutaneous injections. The newer Egrifta WR (F8 formulation), approved by the FDA in March 2025, requires only weekly reconstitution and uses less than half the injection volume -- a meaningful improvement for long-term adherence.
How Tesamorelin Compares to Other Approaches
Tesamorelin occupies a unique position in the treatment of HIV lipodystrophy. Here is how it stacks up against alternatives that have been studied:
| Approach | VAT Reduction | Glucose Effects | Subcutaneous Fat | FDA Approved |
|---|---|---|---|---|
| Tesamorelin | 15-18% | Neutral to mild risk | Preserved | Yes |
| Recombinant GH (high-dose) | 20-40% | Insulin resistance | May worsen wasting | No (for lipodystrophy) |
| Metformin | Modest | Improves | May worsen wasting | No (for lipodystrophy) |
| Diet and exercise | Variable | Improves | Variable | N/A |
| Semaglutide (GLP-1 RA) | Under study | Improves | Reduces | No (for lipodystrophy) |
The selectivity of tesamorelin -- reducing visceral fat while sparing subcutaneous stores and limb fat -- is its primary advantage over approaches like high-dose growth hormone, which can worsen the subcutaneous fat wasting that many HIV patients already experience.
For readers interested in how different peptides affect fat loss through various mechanisms, our best peptides for fat loss guide provides a broader comparison.
Summary of Key Trial Data
| Trial | Year | N | Duration | VAT Reduction | Key Finding |
|---|---|---|---|---|---|
| Falutz (NEJM) | 2007 | 412 | 26 weeks | ~15% | Proof-of-concept; selective visceral fat loss |
| LIPO-010 (Phase III) | 2007-2008 | 412 | 26 + 26 weeks | ~15% | Pivotal registration trial |
| CTR-1011 (Phase III) | 2007-2008 | 404 | 26 + 26 weeks | ~10.9% | Second pivotal registration trial |
| Pooled Analysis (JCEM) | 2010 | 806 | 26-52 weeks | -15.4% | Confirmed consistency; lipid improvements |
| Stanley (Lancet HIV) | 2019 | 61 | 12 months | N/A (liver focus) | 37% reduction in hepatic fat; prevented fibrosis |
FAQ
How quickly does tesamorelin reduce visceral fat?
The Phase III trials measured outcomes at 26 weeks, and significant reductions were apparent by that point. IGF-1 changes appeared as early as 13 weeks. The drug works gradually through its stimulation of endogenous growth hormone -- expect weeks to months, not days.
Does tesamorelin cause weight loss?
Not meaningfully. Tesamorelin redistributes body composition by reducing visceral fat while preserving lean mass. Total body weight may not change much. The primary benefit is metabolic, not a number on the scale.
Can tesamorelin be combined with other peptides?
The clinical trials studied tesamorelin as monotherapy. Combining it with peptides like CJC-1295 or other GHRH analogs has not been evaluated in controlled studies and could compound IGF-1 elevation. Our peptide stacking guide discusses general principles of combination use.
Is tesamorelin only for people with HIV?
The FDA approval is specifically for HIV-associated lipodystrophy. While there is growing interest in tesamorelin for metabolic syndrome, NAFLD, and age-related visceral fat accumulation in the general population, it is not approved for these uses. Off-label use occurs but lacks the rigorous trial data available for the HIV indication.
What about the diabetes risk?
The odds ratio of 3.3-3.6 for developing diabetes is real and should not be dismissed. However, this needs context: the absolute numbers were small (5% vs. 1% for elevated HbA1c), and the comparison group had HIV lipodystrophy, which already carries elevated metabolic risk. Regular glucose monitoring during treatment is strongly recommended.
The Bottom Line
Tesamorelin has the most robust clinical evidence base of any peptide used for visceral fat reduction. Two large Phase III trials, a pooled analysis of over 800 patients, 52 weeks of extension data, and a follow-up liver fat study all point to a consistent conclusion: tesamorelin selectively reduces visceral fat by 15-18%, improves lipid profiles, and now appears to reduce liver fat in HIV patients with NAFLD.
The drug's limitations are equally clear. Effects reverse upon discontinuation. It requires ongoing daily injections (though the newer weekly reconstitution formulation helps). The diabetes risk signal, while small in absolute terms, warrants monitoring. And long-term cardiovascular outcomes data remain incomplete -- the FDA's required 10-year observational study is still ongoing.
For the specific population it was designed to help -- HIV patients with excess visceral fat from antiretroviral therapy -- the clinical evidence supports tesamorelin as a meaningful treatment option. It remains the only FDA-approved therapy for this indication, and the newer studies on liver fat and inflammatory markers suggest its benefits extend beyond what the original trials measured.
References
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Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine. 2007;357(23):2359-2370. PubMed
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Falutz J, Allas S, Mamputu JC, et al. Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation. AIDS. 2008;22(14):1719-1728.
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Falutz J, Potvin D, Mamputu JC, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension. JAIDS. 2010;53(3):311-322. PubMed
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Falutz J, Mamputu JC, Potvin D, et al. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. Journal of Clinical Endocrinology & Metabolism. 2010;95(9):4291-4304. PubMed
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Stanley TL, Feldpausch MN, Oh J, et al. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. 2014;312(4):380-389.
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Stanley TL, Fourman LT, Feldpausch MN, et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. The Lancet HIV. 2019;6(12):e821-e830. PubMed
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Fourman LT, Billingsley JM, Agyapong G, et al. Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD. JCI Insight. 2020;5(16):e140134. PMC
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Hadigan C, Corcoran C, Basgoz N, et al. Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clinical Infectious Diseases. 2012;54(11):1642-1651. PMC