Tesamorelin

Also known as: Egrifta, Egrifta SV, Egrifta WR, TH9507, TH-9507, Tesamorelin acetate

Evidence: Clinical

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Overview

Synthetic GHRH(1-44) analog, FDA-approved 2010 (Egrifta) for excess abdominal fat in HIV lipodystrophy; cut visceral fat about 15% vs placebo over 26 weeks in two phase 3 RCTs (n=806).

Tesamorelin (TH9507) is human GHRH(1-44) with a trans-3-hexenoyl group on the N-terminal tyrosine that resists dipeptidyl peptidase cleavage. The FDA approved it on 10 Nov 2010 (Egrifta, Theratechnologies) to reduce excess abdominal fat in HIV-infected adults with lipodystrophy; it has no non-HIV indication. In the pooled phase 3 trials (n=806), 2 mg SC daily for 26 weeks reduced visceral adipose tissue by 15.4% relative to placebo, lowered triglycerides, and left abdominal subcutaneous fat unchanged; the loss reversed within 26 weeks of stopping (Falutz 2010). Smaller RCTs showed reductions in liver fat (Stanley 2014, n=50; Stanley 2019, n=61). A 20-week RCT in 152 older adults with and without mild cognitive impairment found improved executive function and verbal memory (Baker 2012). Current presentations are Egrifta SV (1.4 mg daily) and Egrifta WR (1.28 mg daily).

Benefits

Visceral fat reduction (human RCT, n=806), triglyceride and cholesterol/HDL improvement (human RCT), liver fat reduction (human RCT, n=50 and n=61), IGF-1 increase (human RCT), cognitive test gains in older adults and MCI (human RCT, n=152)

Dosing reference

Research dose: 1.28-2 mg SC once daily per FDA labels (Egrifta 2 mg; Egrifta SV 1.4 mg; Egrifta WR 1.28 mg); phase 3 trials used 2 mg daily
Range: 1280 to 2000 mcg, 1x daily
Reconstitution: 2 mL bacteriostatic water
Common vial sizes: 2 mg, 5 mg

Subcutaneous once daily (abdomen). Label contraindications: disruption of the hypothalamic-pituitary axis, active malignancy, pregnancy, hypersensitivity. Visceral fat loss reversed within 26 weeks of stopping in the phase 3 extension (Falutz 2010). Fasting glucose rose transiently at 2 weeks in one RCT (Stanley 2014). Reconstitution: Egrifta WR 11.6 mg vial in 1.3 mL bacteriostatic water (8 mg/mL).

Mechanism

Tesamorelin is GHRH(1-44) with an N-terminal trans-3-hexenoyl modification that slows dipeptidyl peptidase IV cleavage (Ferdinandi 2007). It binds the pituitary GHRH receptor and increases pulsatile GH secretion with preserved IGF-1 negative feedback; IGF-1 rose 81% over 26 weeks in the phase 3 trial (Falutz 2007). Visceral fat falls while abdominal subcutaneous fat does not, consistent with GH-driven lipolysis of visceral depots (Falutz 2010). Reductions in liver fat seen in two RCTs are proposed to follow the visceral fat change (Stanley 2014; Stanley 2019).

Evidence

Clinical: at least one published human trial or an approved drug

Phase 3 RCT, n=412: visceral fat -15.2% vs +5.0% placebo over 26 weeks; triglycerides -50 mg/dL; IGF-1 +81% (Falutz et al., 2007)
Pooled phase 3, n=806: VAT treatment effect -15.4%, abdominal SC fat unchanged, effect maintained to 52 weeks and lost after switching to placebo (Falutz et al., 2010)
RCT, n=50: VAT -34 cm2 and liver fat reduced over 6 months; transient fasting glucose rise at 2 weeks (Stanley et al., 2014)
RCT, n=61: reduced hepatic fat fraction and prevented fibrosis progression in HIV-associated NAFLD over 12 months (Stanley et al., 2019)
RCT, n=152: 20 weeks improved executive function and verbal memory in older adults with and without MCI (Baker et al., 2012)
Human-trial status: FDA-approved 10 Nov 2010 (Egrifta, NDA 022505) for excess abdominal fat in HIV lipodystrophy; Egrifta SV and WR presentations followed; not approved for any non-HIV indication

References

Side effects

Label (>5%): arthralgia, injection-site erythema and pruritus, pain in extremity, peripheral edema, myalgia. Phase 3 trials: adverse events did not differ from placebo overall but more tesamorelin patients withdrew for an adverse event (Falutz 2007); no clinically meaningful glucose change at 26 or 52 weeks in the pooled analysis (Falutz 2010), though one small RCT saw a transient fasting-glucose rise (Stanley 2014). Hypersensitivity reactions are listed on the label.

Storage

Storage: 20-25C for Egrifta SV and WR vials (label); research-grade lyophilized vials are commonly refrigerated 2-8C (general guidance)
Lyophilized: 2+ years at room temp, 3+ years refrigerated
Reconstituted: Label: Egrifta SV is used immediately after reconstitution; Egrifta WR is discarded 7 days after mixing (20-25C). 28-30 days refrigerated is general peptide guidance, not label

Pharmacology

Half-life: ~8-11 min (human, SC; current Egrifta SV and WR labels)
Bioavailability: <4% absolute (human, SC 2 mg; FDA label)
Molecular weight: 5135.89 Da
Sequence: [trans-3-hexenoyl]YADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGARARL[NH2]