How Tesamorelin Affects IGF-1

Tesamorelin raises IGF-1 through GHRH receptor activation:

1. GHRH receptor agonism: Tesamorelin is a synthetic analog of GHRH(1-44) with a trans-3-hexenoic acid modification that extends its half-life (26-38 minutes vs. minutes for native GHRH). It stimulates GH release by activating the GHRH receptor on pituitary somatotrophs.
2. Pulsatile GH pattern: Unlike MK-677, tesamorelin preserves the natural pulsatile pattern of GH secretion. It amplifies existing GH pulses rather than creating continuous stimulation.
3. Hepatic IGF-1 synthesis: The amplified GH pulses drive hepatic IGF-1 production in a dose-dependent manner.
4. Feedback regulation: Tesamorelin's GH release is subject to normal somatostatin feedback, which provides a physiological ceiling on IGF-1 elevation and contributes to its favourable metabolic profile.

Standard dose (2 mg/day, subcutaneous):

• IGF-1 increases approximately 81% from baseline (Falutz et al., 2007, NEJM)
• This is a substantial elevation, exceeding most other peptides at standard doses
• The FDA trial was conducted in HIV-positive patients with lipodystrophy; response in otherwise healthy athletes may differ

Metabolic co-effects (uniquely favourable):

• Triglycerides decreased by approximately 50 mg/dL
• Total cholesterol-to-HDL ratio improved
• No significant worsening of fasting glucose or HbA1c
• Visceral fat reduced by 15.2%

Timeline: IGF-1 elevation begins within the first week and is well-established by 4 weeks.

Baseline: IGF-1, fasting glucose, triglycerides, TSH, free T4.

During use:

• IGF-1 at 4 weeks, then every 3 months
• Triglycerides at 3 months (to confirm the lipid benefit)
• TSH at 3-6 months (class-effect precaution for GHRH analogs)
• Fasting glucose quarterly (expected to remain stable, but confirm)

Key advantage: Tesamorelin has the largest evidence base of any peptide in this class (Phase III RCTs, FDA approval), making its monitoring profile the most well-characterised.

Optimising the response:

• Inject subcutaneously at a consistent time daily
• Abdominal injection is the standard site (matching the FDA trial protocol)
• Store reconstituted tesamorelin refrigerated and use within 14 days

If IGF-1 is excessively elevated:

• Tesamorelin is typically available only at 2 mg dose; dose reduction requires splitting
• Consider alternate-day dosing to reduce average IGF-1 exposure while maintaining benefits

Lipid benefits:

• The triglyceride reduction is a genuine clinical benefit, particularly for AAS users who frequently present with elevated triglycerides
• Monitor triglycerides to confirm this benefit is being realised