What are the benefits and mode of action of Tesamorelin (growth hormone-releasing factor) in reducing excess abdominal fat in HIV-infected patients with lipodystrophy?

Tesamorelin Benefits and Mode of Action for HIV-Associated Lipodystrophy

Tesamorelin effectively reduces excess abdominal visceral adipose tissue (VAT) in HIV-infected patients with lipodystrophy by stimulating the synthesis and release of endogenous growth hormone, with significant reductions of approximately 15-17% after 6 months of treatment. 1, 2

Mechanism of Action

• Tesamorelin is a synthetic analog of human growth hormone-releasing hormone (GHRH) that stimulates the synthesis and release of endogenous growth hormone 1
• By increasing endogenous growth hormone levels, tesamorelin specifically targets visceral adipose tissue accumulation without significantly affecting subcutaneous adipose tissue 2
• This selective action on visceral fat helps address the characteristic central fat accumulation seen in HIV-associated lipodystrophy 3

Clinical Benefits

Primary Benefit: Reduction in Visceral Adipose Tissue

• Reduces visceral adipose tissue (VAT) by approximately 15.4% after 26 weeks of treatment compared to placebo 3
• Maintains VAT reduction for up to 52 weeks with continued treatment (17.5% reduction from baseline) 3
• Does not significantly affect subcutaneous adipose tissue, preserving this important fat compartment 3
• Discontinuation of therapy results in reaccumulation of VAT, indicating the need for continued treatment 2

Metabolic Benefits

• Significantly decreases triglyceride levels (12.3% reduction vs. placebo at 26 weeks) 3
• Improves cholesterol to HDL ratio (7.2% reduction vs. placebo) 3
• Does not cause clinically meaningful changes in glucose parameters during treatment periods of up to 52 weeks 3

Body Image and Quality of Life Benefits

• Improves body image parameters including:
  • Reduced belly appearance distress 3
  • Improved patient rating of belly profile 3
  • Improved physician rating of belly profile 3
• These improvements in body image may potentially improve self-image and quality of life for patients with HIV-associated lipodystrophy 1

Predictors of Treatment Response

• Patients with metabolic syndrome (as defined by NCEP criteria), elevated triglyceride levels >1.7 mmol/L, and white race show better response to tesamorelin after 6 months of therapy 4
• The odds of achieving a VAT reduction to <140 cm² (a level associated with lower risk of adverse health outcomes) is 3.9 times greater with tesamorelin than with placebo 4

Safety Profile

• Generally well tolerated with treatment-emergent serious adverse events occurring in <4% of patients during 26 weeks of therapy 1
• Most common adverse events are:
  • Injection-site reactions 1
  • Events typically associated with growth hormone therapy (arthralgia, headache, peripheral edema) 1, 2
• No clinically meaningful differences in glucose parameters observed between treatment and placebo groups at 26 and 52 weeks 3

Clinical Context

• HIV-associated lipodystrophy affects approximately 25-75% of patients on antiretroviral therapy (ART) 5
• Fat accumulation is commonly seen in the abdomen, dorsocervical fat pad, and breasts, with prevalence increasing with duration of antiretroviral therapy 5
• Prior to tesamorelin, no clearly effective therapy for fat accumulation in HIV-associated lipodystrophy was available 5
• Lipodystrophy is associated with metabolic abnormalities including serum dyslipidemias and glucose intolerance 5

Important Considerations and Limitations

• Tesamorelin is the first and only FDA-approved treatment specifically for reduction of excess abdominal fat in patients with HIV-associated lipodystrophy 1, 2
• Benefits are maintained only with continued therapy; discontinuation leads to reaccumulation of VAT 2
• Long-term clinical experience beyond 52 weeks is needed to further assess the benefits and risks of therapy 1
• Treatment should target patients with significant central fat accumulation, particularly those with metabolic syndrome or elevated triglycerides who may show better response 4