Tesamorelin: A Growth Hormone-Releasing Factor Analog
Tesamorelin is a synthetic analog of human growth hormone-releasing hormone (GHRH) that stimulates the synthesis and release of endogenous growth hormone, primarily used for reducing excess visceral adipose tissue in HIV-associated lipodystrophy. 1, 2
Mechanism of Action
- Tesamorelin acts as a growth hormone-releasing factor (GRF) analog that stimulates the pituitary gland to produce and release endogenous growth hormone 1
- Unlike direct growth hormone administration, tesamorelin works through the body's natural regulatory pathway for growth hormone production 2
- It specifically targets the hypothalamic-pituitary axis to increase growth hormone secretion 3
FDA-Approved Indications
- Tesamorelin is the first and only FDA-approved treatment for reducing excess abdominal fat in patients with HIV-associated lipodystrophy 4
- It received FDA approval in November 2010 specifically for this indication 4
Clinical Efficacy
- In two 26-week clinical trials, subcutaneous tesamorelin effectively reduced visceral adipose tissue (VAT) in patients with HIV-associated central fat accumulation 2
- The reduction in VAT was maintained in patients who continued tesamorelin treatment for up to 52 weeks 1
- Discontinuation of therapy resulted in reaccumulation of VAT, indicating ongoing treatment is necessary to maintain benefits 2
- Tesamorelin therapy was also associated with significant improvements in other body composition measures including trunk fat and waist circumference 1
- Patients receiving tesamorelin had 3.9 times greater odds of achieving VAT reduction to <140 cm² (a level associated with lower health risks) compared to placebo 5
Patient Selection and Response Predictors
- Individuals with metabolic syndrome (as defined by National Cholesterol Education Program criteria), elevated triglyceride levels, or white race were most likely to experience significant VAT reductions after 6 months of tesamorelin treatment 5
- The presence of these factors should be considered when selecting patients for therapy 5
Administration and Dosing
- Tesamorelin is administered as a subcutaneous injection 1
- The standard dose used in clinical trials was 2 mg daily 5
Safety and Adverse Effects
- Tesamorelin was generally well tolerated in clinical trials, with treatment-emergent serious adverse events occurring in less than 4% of patients during 26 weeks of therapy 1
- Common adverse effects include:
- Monitoring should include assessment of IGF-1 levels as recommended by the Endocrine Society 3
- Glucose metabolism should be closely monitored due to potential effects on insulin sensitivity 3
Limitations and Considerations
- Long-term clinical experience is needed to further assess the benefits and risks of therapy 2
- Discontinuation of therapy results in reaccumulation of visceral fat, suggesting that ongoing treatment is necessary to maintain benefits 1
- Unlike direct growth hormone administration which has been studied in COPD patients with mixed results, tesamorelin has not been extensively studied for conditions other than HIV-associated lipodystrophy 6
- In contrast to anabolic steroids which directly increase muscle mass and strength, tesamorelin works through stimulating endogenous growth hormone production 6
Potential Use in Other Conditions
- While growth hormone and growth hormone-releasing factors have been investigated in other conditions characterized by muscle wasting or cachexia, such as COPD, the evidence for tesamorelin specifically in these conditions is limited 6
- For patients with short bowel syndrome, GLP-2 analogs like teduglutide are suggested as first-choice growth factor treatment rather than growth hormone-releasing factors like tesamorelin 6
Tesamorelin represents an important therapeutic option for patients with HIV-associated lipodystrophy, with demonstrated efficacy in reducing visceral adiposity and potentially improving body image and metabolic parameters.