K4 Elite
K4 Elite
Tesamorelin (TH9507) is a synthetic analogue of growth hormone-releasing hormone (GHRH 1-44) that is FDA-approved as Egrifta / Egrifta SV / Egrifta WR for reduction of excess abdominal fat in HIV-infected adults with lipodystrophy. Its evidence base consists of two 26-week Phase 3 placebo-controlled trials (806 randomised) with 26-week safety extensions, a 6-month NIH-funded RCT examining visceral and liver fat (Stanley et al., JAMA 2014), and the FDA prescribing information, which carries contraindications (hypothalamic-pituitary axis disruption, active malignancy, pregnancy, hypersensitivity) and warnings on IGF-1 elevation, fluid retention and glucose intolerance.
Each row records what a published study did: who it enrolled, the regimen it administered to those subjects, and what it reported. These are historical study descriptions, not protocols to follow.
| Study | Population | Regimen as reported | Primary findings |
|---|---|---|---|
| Falutz et al., NEJM 2007 (Phase 3) Registry: NCT00123253
|
HIV-infected patients with accumulation of abdominal fat on antiretroviral therapy (n=412; 86% men) | Patients were randomly assigned to a daily subcutaneous injection of tesamorelin 2 mg or placebo for 26 weeks. | Visceral adipose tissue decreased by 15.2% with tesamorelin and increased by 5.0% with placebo; IGF-I rose 81.0% versus a 5.0% fall; adverse events did not differ significantly, but more tesamorelin patients withdrew because of an adverse event; no significant differences in glycaemic measures. |
| Falutz et al., J Clin Endocrinol Metab 2010 (pooled Phase 3 with 26-week extension) | Antiretroviral-treated HIV patients with excess abdominal fat (n=806; 543 tesamorelin, 263 placebo) | Patients received tesamorelin 2 mg or placebo subcutaneously daily for 26 weeks; at week 26 tesamorelin patients were re-randomised to tesamorelin or placebo and placebo patients switched to tesamorelin for a further 26 weeks. | At week 26 VAT changed by -24 vs +2 cm2 (treatment effect -15.4%); mean IGF-I increased 108 vs -7 ng/mL; no clinically meaningful between-group differences in glucose parameters at weeks 26 and 52. |
| Stanley et al., JAMA 2014 (single-centre RCT) Registry: NCT01263717
|
Antiretroviral-treated HIV-infected men and women with abdominal fat accumulation at Massachusetts General Hospital (n=50 randomised; 48 treated) | Participants received tesamorelin 2 mg (n=28) or placebo (n=22) subcutaneously daily for 6 months. | Tesamorelin reduced visceral adipose tissue (treatment effect -42 cm2) and liver fat (net -2.9% lipid-to-water); fasting glucose rose by a treatment effect of 7 mg/dL at 2 weeks but 6-month fasting and 2-hour glucose changes were not significant. |
Effects recorded in the cited reports. Frequencies are those the source reported, in the population that source studied.
| Effect | Frequency / context | Source |
|---|---|---|
| Injection-site reactions (erythema, pruritus, rash, urticaria, pain, swelling, irritation, haemorrhage) | 17% with Egrifta vs 6% placebo during the 26-week phase of the combined Phase 3 studies (Egrifta SV label, Table 1). | EGRIFTA SV (tesamorelin) — Prescribing Information (DailyMed) ↗ |
| Arthralgia | 13% vs 11% placebo (Egrifta SV label, Table 1). | EGRIFTA SV (tesamorelin) — Prescribing Information (DailyMed) ↗ |
| Pain in extremity | 6% vs 5% placebo (Egrifta SV label, Table 1). | EGRIFTA SV (tesamorelin) — Prescribing Information (DailyMed) ↗ |
| Myalgia | 6% vs 2% placebo (Egrifta SV label, Table 1). | EGRIFTA SV (tesamorelin) — Prescribing Information (DailyMed) ↗ |
| Peripheral oedema | 6% vs 2% placebo (Egrifta SV label, Table 1); fluid retention including oedema, arthralgia and carpal tunnel syndrome is a labelled warning. | EGRIFTA SV (tesamorelin) — Prescribing Information (DailyMed) ↗ |
| Paresthesia / hypoesthesia | Paresthesia 5% vs 2%; hypoesthesia 4% vs 2% placebo (Egrifta SV label, Table 1). | EGRIFTA SV (tesamorelin) — Prescribing Information (DailyMed) ↗ |
| Rash / hypersensitivity reactions | Rash 4% vs 2% placebo; hypersensitivity reactions (rash, urticaria) were among the most commonly reported reactions and are a labelled warning (Egrifta SV label). | EGRIFTA SV (tesamorelin) — Prescribing Information (DailyMed) ↗ |
| Carpal tunnel syndrome | 1% vs 0% placebo (Egrifta SV label, Table 1). | EGRIFTA SV (tesamorelin) — Prescribing Information (DailyMed) ↗ |
| New-onset diabetes (HbA1c >=6.5%) | 5% with Egrifta vs 1% placebo (hazard ratio 3.3, CI 1.4-9.6) in the clinical trials, from a mean baseline HbA1c of 5.3% (Egrifta SV label). | EGRIFTA SV (tesamorelin) — Prescribing Information (DailyMed) ↗ |
| Elevated IGF-1 | Mean IGF-1 change at week 26 was +107 and +108 ng/mL in Studies 1 and 2 vs -15 and +3 ng/mL with placebo (label Table 3); IGF-1 rose 81.0% in Falutz 2007. The label advises monitoring IGF-1 and considering discontinuation with persistent elevation. | EGRIFTA SV (tesamorelin) — Prescribing Information (DailyMed) ↗ |
| Anti-tesamorelin antibodies | IgG antibodies detected in 50% of patients after 26 weeks and 47% after 52 weeks; 85% among those with hypersensitivity reactions; ~60% of antibody-positive patients showed cross-reactivity to endogenous GHRH (Egrifta SV label). | EGRIFTA SV (tesamorelin) — Prescribing Information (DailyMed) ↗ |
| Transient fasting glucose rise | Treatment effect +7 mg/dL at 2 weeks (P=.03) with no significant difference at 6 months (Stanley et al., JAMA 2014). | Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial ↗ |
| Withdrawal due to adverse events | More patients in the tesamorelin group than placebo withdrew because of an adverse event, although overall adverse-event rates did not differ significantly (Falutz et al., NEJM 2007). | Metabolic effects of a growth hormone-releasing factor in patients with HIV ↗ |
Interactions documented in trial reports, prescribing information or pharmacology references.
| Agent | Type | Note | Source |
|---|---|---|---|
| Drugs metabolised by cytochrome P450 (e.g., corticosteroids, sex steroids, anticonvulsants, cyclosporine) | pharmacokinetic (GH-mediated CYP450 modulation) | The label states that GH may alter clearance of CYP450-metabolised compounds and advises monitoring for potential interactions; co-administration with simvastatin (a CYP3A substrate) had no significant effect on simvastatin pharmacokinetics in healthy subjects. | EGRIFTA SV (tesamorelin) — Prescribing Information, section 7.1 (DailyMed) ↗ |
| Glucocorticoid replacement (cortisone acetate, prednisone) | pharmacodynamic (11beta-HSD-1 inhibition by GH) | Patients on glucocorticoid replacement for hypoadrenalism may require increased maintenance or stress doses after starting tesamorelin, particularly with cortisone acetate and prednisone, whose activation depends on 11beta-HSD-1. | EGRIFTA SV (tesamorelin) — Prescribing Information, section 7.2 (DailyMed) ↗ |
Exclusions and label contraindications recorded in the cited sources.