Tesamorelin is a synthetic analogue of human growth hormone-releasing hormone that stimulates the synthesis and release of endogenous growth hormone. Marketed as Egrifta and administered via subcutaneous injection, it received FDA approval in November 2010 as the first and only treatment specifically indicated for reducing excess abdominal fat in patients with HIV-associated lipodystrophy. Phase III randomized controlled trials demonstrate that tesamorelin effectively reduces visceral adipose tissue and waist circumference over 26 weeks, with benefits maintained through 52 weeks of continued treatment. However, discontinuation results in reaccumulation of visceral adipose tissue, indicating the need for indefinite therapy. The drug selectively targets visceral fat without clinically significant effects on subcutaneous adipose tissue and demonstrates minimal adverse effects on glucose tolerance and lipid parameters.
The safety profile appears favorable in the short-to-medium term, with serious adverse events occurring in less than 4% of patients during 26 weeks of therapy and common adverse events limited primarily to injection-site reactions and growth hormone-associated effects such as arthralgia, headache, and peripheral edema. However, multiple sources identify the lack of long-term safety and adherence data as a significant limitation, which is particularly relevant given the requirement for continuous treatment. Limited data currently support off-label applications, and other potential indications beyond HIV-associated lipodystrophy appear less promising. Key evidence gaps include optimal dosing protocols, long-term cardiovascular and metabolic outcomes, and whether treatment duration beyond 52 weeks maintains efficacy and tolerability.
Methods
We analyzed 5 sources from an initial pool of 50, using 8 screening criteria. Each paper was reviewed for 8 key aspects.
- Study Population: Does the study involve human adult participants (≥18 years old)?
- Study Design: Is this a clinical trial (Phase I-IV), observational study (cohort, case-control, cross-sectional), systematic review/meta-analysis, or case series with ≥5 patients?
- Relevant Outcomes: Does the study report on mechanism of action, pharmacokinetics, pharmacodynamics, efficacy, safety, or clinical outcomes of tesamorelin?
- Clinical Applications: Does the study investigate tesamorelin for approved indications (HIV-associated lipodystrophy) or investigational applications?
- Human Clinical Evidence: Is this a human clinical study (not an animal study, in vitro study, or preclinical research)?
- Study Quality and Type: Is this a peer-reviewed study with original data (not a case report, case series with <5 patients, conference abstract, letter, editorial, or commentary without original data)?
- Specificity: Does the study include tesamorelin data (not focusing solely on other growth hormone-releasing hormone analogs without tesamorelin data)?
We considered all screening questions together and made a holistic judgement about whether to screen in each paper.
This review includes five sources examining tesamorelin for HIV-associated lipodystrophy. All sources had only abstracts available for analysis.
| Source | Study Type |
| Dhillon et al. | Review |
| Dhillon et al. | Review |
| Spooner et al. | Review of Phase III Clinical Trials |
| Leung et al. | Review |
| Wang et al. | Randomized controlled Trial (Phase III) |
Characteristics
Tesamorelin is a synthetic analogue of human growth hormone-releasing hormone (GHRH), also described as a growth hormone-releasing factor analogue.
The mechanism of action involves stimulating the synthesis and release of endogenous growth hormone. This distinguishes tesamorelin from recombinant human growth hormone by working through the body’s natural growth hormone release pathways rather than providing exogenous hormone directly.
Tesamorelin is administered via subcutaneous injection. Treatment duration in clinical trials was 26 weeks with extension phases continuing until week 52. However, specific dosing recommendations and frequency were not detailed in the available abstracts. Optimal therapeutic dosing and treatment duration remain incompletely characterized.
Indication
Tesamorelin is the first and only treatment specifically indicated for the reduction of excess abdominal fat in patients with HIV-associated lipodystrophy. This condition, also referred to as HIV-associated lipohypertrophy, manifests as central fat accumulation with specific targets including excess abdominal fat, visceral adipose tissue, trunk fat, and increased waist circumference.
The treatment addresses not only physical manifestations but also impacts body image parameters, particularly belly image distress. The patient population consists of individuals with HIV infection experiencing significant lipodystrophy, specifically those with visceral fat accumulation and associated metabolic complications.
| Outcome Measure | Findings | Duration |
| Visceral adipose tissue (VAT) reduction | reductions | 26 weeks |
| Waist circumference | Significant decrease | 26 weeks |
| Trunk fat | Significant improvements | Not specified |
| Body image parameters | General improvements; significant improvement in subjective measures | 26 weeks |
| Lipid parameters | Improvement | Not specified |
| Subcutaneous adipose tissue | No clinically significant effect | 26 weeks |
| Visceral fat (Phase III Trial) | Positive effect on reduction | Not specified |
The efficacy data demonstrate selective action on visceral adiposity. While tesamorelin effectively reduced visceral adipose tissue in well-designed 26-week clinical trials, it did not affect subcutaneous adipose tissue to a clinically significant extent. Two Phase 3 clinical trials and their pooled analyses demonstrated significant decreases in both waist circumference and visceral adipose tissue after 26 weeks of treatment.
The benefits of tesamorelin showed clear reversibility patterns. While reductions in VAT were maintained through week 52 in patients who continued treatment during extension phases, discontinuation of therapy resulted in reaccumulation of visceral adipose tissue. This finding indicates that continuous treatment is necessary to maintain therapeutic benefits.
Secondary efficacy outcomes included improvements in trunk fat and waist circumference, as well as subjective body image parameters. Extension phase data confirmed maintenance of VAT improvements without adverse impact on blood glucose and lipid parameters. One review specifically noted improvement in lipid parameters alongside visceral adipose tissue reduction.
Tolerability
| Parameter | Findings |
| Overall tolerability | Generally well tolerated; good safety profile |
| Serious adverse events | <4% of patients during 26 weeks |
| Common adverse events | Injection-site reaction, arthralgia, headache, peripheral edema |
| Glucose tolerance | Minimal adverse effects |
| Blood glucose parameters | No adverse impact during extension phases |
| Lipid parameters | No adverse impact during extension phases |
| Long-term safety data | Limited; further assessment needed |
Tesamorelin demonstrated favorable short-term tolerability across clinical trials. Treatment-emergent serious adverse events occurred in less than 4% of patients during 26 weeks of therapy. The most commonly reported adverse events were injection-site reactions and effects known to be associated with growth hormone therapy, including arthralgia, headache, and peripheral edema.
Metabolic parameters showed reassuring profiles. The drug demonstrated minimal adverse effects on glucose tolerance and did not adversely impact blood glucose or lipid parameters during 26-week extension phases. However, multiple sources noted that long-term safety and adherence data remain lacking, representing a gap in the evidence base. Specific information regarding treatment discontinuation rates due to adverse events, contraindications, warnings, interactions, and special populations considerations was not provided in the available abstracts.
Investigational application
Limited data currently support off-label uses of tesamorelin. The primary investigational focus remains on HIV-associated lipohypertrophy, specifically for reducing visceral fat accumulation. Ongoing research directions include determination of optimal therapeutic dosing and treatment duration, which remain incompletely defined.
A key area of future investigation involves whether treatment with GHRH-analogues will translate into improved long-term metabolic and cardiovascular outcomes. While short-term trials demonstrated improvements in visceral adiposity and some metabolic parameters, the long-term clinical significance of these changes requires further study.
Other potential indications for tesamorelin beyond HIV-related lipodystrophy have been explored but appear less promising based on available data. The development rationale for GHRH analogues like tesamorelin stemmed from seeking better-tolerated alternatives to recombinant human growth hormone for conditions associated with relative growth hormone deficiency. However, the clinical evidence remains most robust for the HIV-associated lipodystrophy indication.
Synthesis
The evidence base for tesamorelin in HIV-associated lipodystrophy demonstrates consistent efficacy for the primary outcome of visceral adipose tissue reduction. All sources examining this outcome reported positive effects, with convergent findings across Phase III randomized controlled trials and their subsequent reviews. The mechanistic basis—stimulation of endogenous growth hormone release—provides a biological rationale for the observed selective effect on visceral rather than subcutaneous fat.
The requirement for continuous treatment represents an important clinical consideration. The clear demonstration that discontinuation leads to VAT reaccumulation indicates that tesamorelin addresses symptoms rather than underlying pathophysiology. This necessitates indefinite treatment for sustained benefit, raising questions about long-term adherence, cost-effectiveness, and safety that the current evidence base cannot fully address.
The safety profile appears acceptable for short-to-medium term use (26-52 weeks), with serious adverse events affecting less than 4% of patients and reassuring metabolic parameters. However, multiple sources explicitly acknowledge that long-term safety data remain limited, representing the primary evidence gap given the need for continuous therapy. The absence of adverse effects on glucose tolerance and lipid parameters during available follow-up periods is encouraging but requires validation over years rather than months.
For clinical application, tesamorelin provides a targeted option for patients with HIV-associated lipodystrophy experiencing significant visceral fat accumulation. The selective action on visceral versus subcutaneous adipose tissue means patients should be counseled that treatment addresses central fat accumulation specifically. The improvements in body image parameters suggest meaningful patient-reported outcomes beyond objective measurements, though the magnitude and clinical significance of these improvements across diverse patient populations require further characterization.
References
Sohita Dhillon (2011). Tesamorelin. Drugs
Sohita Dhillon (2011). Spotlight on Tesamorelin in HIV-Associated Lipodystrophy. BioDrugs
Ying Wang, B. Tomlinson (2009). Tesamorelin, a human growth hormone releasing factor analogue
Linda M. Spooner, J. L. Olin (2012). Tesamorelin: A Growth Hormone-Releasing Factor Analogue for HIV-Associated Lipodystrophy. The Annals of Pharmacotherapy
Vivien Leung, M. Glesby (2011). Pathogenesis and treatment of HIV lipohypertrophy. Current Opinion in Infectious Diseases