Mechanism of Action
Competitive antagonism of functional GHR dimerization. Blocks GH action at receptor level — does not suppress GH secretion, blocks peripheral action. Mechanistic counterpoint to GH secretagogues.
Clinical Use
Acromegaly, particularly when surgery and somatostatin analogs are insufficient or not tolerated.
Contraindications
Hepatic disease (monitor LFTs throughout therapy). Tumor growth monitoring required.
Evidence Summary
20+ years safety/efficacy data. ACROSTUDY global registry (n=2,221) is longest acromegaly registry. 97% IGF-1 normalization at 12+ months without tachyphylaxis.
Key Studies
- 1.Trainer et al., NEJM 2000 — IGF-1 normalization: 54% (10mg), 81% (15mg), 89% (20mg) vs 10% placebo. Long-term: 97% at 12+ months. n=112, Phase III RCT
- 2.Fleseriu et al., ACROSTUDY Final Analysis 2021 — IGF-1 normalization 75.4% at 10 years. Tumor growth 7.1%. Real-world monotherapy 71.7%. n=2,221 global registry
Evidence Gaps
LFT monitoring required throughout treatment. Does not reduce tumor size — GH secretion continues.
Emerging Research
Combination with somatostatin analogs for refractory acromegaly.