Pegvisomant
A pegylated GH-receptor antagonist approved for acromegaly. Unlike secretagogues it blocks GH signalling, lowering IGF-1 in patients with excess GH resistant to other therapies.
01 Overview
Pegvisomant (brand Somavert) is a genetically engineered analogue of human growth hormone that binds the GH receptor but blocks its functional dimerisation, preventing signal transduction. It is the only true GH-receptor antagonist in clinical use and is highly effective at normalising IGF-1 in acromegaly.
It is included in this GH-axis set as the mechanistic mirror of the secretagogues: rather than raising GH output, it neutralises GH action peripherally. It is a well-studied approved biologic dosed by daily subcutaneous injection.
02 Mechanism
Binds the growth hormone receptor and blocks productive receptor dimerisation, preventing downstream signalling and lowering hepatic IGF-1 production.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Acromegaly | 10–30 mg/day | SubQ | After a loading dose; titrated to normalise IGF-1. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Normalises IGF-1Highly effective at bringing IGF-1 into the normal range in acromegaly. | >90% of patients at adequate dose | Clinical | |
| Improves acromegaly symptomsSymptomatic improvement as IGF-1 normalises. | soft-tissue, sweating, fatigue | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Elevated liver enzymesTransaminase elevations, usually reversible. | Moderate | Common | Clinical | |
| Injection-site lipohypertrophyLocalised fat accumulation at injection sites. | Mild | Common | Clinical | |
| Tumour growth (theoretical)Because pituitary GH is not suppressed, adenoma size must be monitored. | Moderate | Rare | Clinical |