Tesamorelin

Tesamorelin is an FDA-approved synthetic analog of growth hormone-releasing hormone (GHRH) marketed under the brand name Egrifta. It represents something unusual in the peptide landscape: a GH-stimulating compound that has achieved full regulatory approval for human use.

The FDA approved Tesamorelin in 2010 specifically for reducing excess abdominal fat in HIV-infected patients with lipodystrophy—a condition where antiretroviral medications cause abnormal fat distribution, particularly accumulation of visceral fat around the abdomen and organs. This specific fat pattern carries metabolic and cardiovascular risks that Tesamorelin helps address.

Why Visceral Fat Matters

Not all fat is equal. Visceral adipose tissue (VAT)—fat surrounding internal organs—is metabolically active and dangerous. It secretes inflammatory compounds, impairs insulin sensitivity, and correlates strongly with cardiovascular disease, diabetes, and metabolic syndrome. Tesamorelin specifically reduces VAT, which is why its benefits extend beyond cosmetic improvement to meaningful health outcomes.

Beyond HIV

While FDA-approved only for HIV lipodystrophy, Tesamorelin's mechanism isn't HIV-specific. Research has explored its use for general visceral obesity, non-alcoholic fatty liver disease (NAFLD), and even cognitive enhancement in aging. The narrow FDA indication reflects pharmaceutical business decisions, not biological limitations of the compound.

Tesamorelin works through the GHRH receptor pathway—different from ghrelin-receptor peptides like Ipamorelin or GHRP-6.

GHRH Receptor Activation

The pituitary gland has specific GHRH receptors that, when stimulated, trigger growth hormone release. Tesamorelin is a modified version of natural GHRH (with a trans-3-hexenoic acid group added for stability) that binds these receptors and stimulates GH secretion.

GH and Fat Metabolism

Growth hormone promotes lipolysis—the breakdown of stored fat for energy. It preferentially affects visceral fat, explaining why Tesamorelin reduces abdominal fat more than subcutaneous fat. GH also helps maintain lean mass during weight loss, improving body composition beyond simple scale weight.

Maintaining Physiological Patterns

Unlike direct HGH injection, Tesamorelin stimulates your own pituitary to release GH. This maintains more natural pulsatile release patterns and allows your body's feedback systems to continue operating. You don't achieve the sustained supraphysiological levels possible with HGH, which may be safer long-term but also means effects are more modest.

IGF-1 Elevation

The GH released in response to Tesamorelin triggers IGF-1 production from the liver. IGF-1 mediates many of GH's effects including its metabolic and potentially cognitive benefits. Clinical trials confirmed Tesamorelin raises IGF-1 levels, though within physiological ranges.

Tesamorelin has robust clinical trial data supporting its FDA approval.

Pivotal HIV Lipodystrophy Trials

The FDA approval was based on two Phase 3 trials enrolling over 800 patients. Results published in the New England Journal of Medicine showed Tesamorelin reduced trunk fat by approximately 15-18% compared to about 1% for placebo. The reduction was specific to visceral fat—limb fat (often already depleted in HIV lipodystrophy) was preserved.

Metabolic Improvements

Beyond fat reduction, trials showed improved lipid profiles: decreased triglycerides and favorable changes in cholesterol markers. Studies also demonstrated reduced liver fat and improved markers of fatty liver disease—significant given NAFLD's health implications.

Cognitive Research

More recent research has explored Tesamorelin's cognitive effects. A 2021 study in the Journal of Clinical Endocrinology & Metabolism found improvements in executive function and verbal memory in healthy older adults receiving Tesamorelin, suggesting benefits beyond body composition.

Long-Term Safety

Follow-up studies confirmed Tesamorelin's safety profile over extended use, though they also showed that benefits don't persist after discontinuation—visceral fat returns toward baseline when treatment stops.

Tesamorelin has established pharmaceutical dosing from its FDA approval.

Standard Dose

2mg subcutaneously once daily—this is the FDA-approved dose used in clinical trials.

Administration

Inject subcutaneously in the abdomen, rotating sites to avoid lipodystrophy at injection locations. The pharmaceutical product (Egrifta) comes with mixing and injection instructions.

Duration

Clinical trials typically ran 6-12 months. Since benefits reverse after stopping, Tesamorelin is generally considered ongoing treatment rather than time-limited therapy.

Monitoring

Regular monitoring of fasting glucose and HbA1c is recommended given GH effects on glucose metabolism. IGF-1 levels can be checked to confirm response.

Tesamorelin's safety profile is well-characterized from clinical trials.

Common Side Effects

Injection site reactions: Most common—erythema, pruritus, irritation. Usually mild and manageable.

Arthralgia: Joint pain, related to GH effects. Often transient.

Peripheral edema: Fluid retention, also GH-related.

Paresthesias: Numbness/tingling, particularly in hands.

Metabolic Effects

Elevated fasting glucose and reduced insulin sensitivity occur in some patients—monitor glucose markers. The effect is generally modest but matters for those with metabolic risk factors.

Contraindications

Active malignancy (GH can promote tumor growth), pregnancy, hypersensitivity to Tesamorelin or mannitol. Caution in diabetes or significant glucose intolerance.