Pegvisomant in managing comorbidities of acromegaly: a review

Acromegaly is a rare endocrine disorder caused by excessive growth hormone secretion, leading to elevated insulin-like growth factor I (IGF-I) levels and complications. While surgery is the first-line treatment, many patients require additional therapies. Pegvisomant, a GH receptor antagonist, has emerged as an effective option, particularly for patients unresponsive to somatostatin receptor ligands. This review synthesizes studies evaluating pegvisomant’s role in managing acromegaly, focusing on its impact on comorbidities and quality-of-life (QoL). Outcomes include IGF-I normalization, cardiovascular and metabolic health, skeletal integrity, and QoL. Pegvisomant consistently shows high efficacy in IGF-I normalization, with rates of 60%–80% in real-world settings and up to 89% in clinical trials. Cardiovascular benefits include reductions in left ventricular mass, blood pressure, and improved vascular function. Metabolic improvements involve better glucose metabolism, especially in diabetic patients, as pegvisomant improves insulin sensitivity by directly blocking GH action, without suppressing insulin secretion. Skeletal outcomes include reduced vertebral fracture risk, while respiratory benefits involve reduced tongue volume and improved obstructive sleep apnea. QoL improves across multiple domains, even in patients with partial biochemical control. Limitations of pegvisomant therapy include the need for higher doses to normalize IGF-I in diabetic patients. Persistent fracture risks linked to disease activity and untreated hypogonadism remain, and slight increases in BMI and LDL cholesterol have been observed. This review underscores pegvisomant’s efficacy in IGF-I normalization and comorbidity management. However, limited studies highlight the need for further research on long-term effects, safety, and combination therapy. Individualized treatment remains key to optimizing outcomes.