Pegvisomant improves glucose metabolism in acromegaly. A meta-analysis of prospective interventional studies

INTRODUCTION: Pegvisomant (PEG) in monotherapy or combined with somatostatin analogs (SSAs) is used to control acromegaly, improving metabolism. However, the metabolic changes induced by PEG have not been systematically reviewed. OBJECTIVE: To address the following questions: does PEG or the combination of PEG and SSAs affect fasting plasma glucose (FPG), glycosylated Hb (HbA1c), glucose load (2-hour oral glucose tolerance test), insulin levels [fasting plasma insulin (FPI)], homeostatic model assessment of insulin resistance (HOMA-I), homeostatic model assessment of β-cell function, lipid profile, or body mass index? Are the effects disease-related or drug-related? DATA SOURCES: Indexed databases up to January 2019. STUDY SELECTION: Prospective interventional trials reporting glycometabolic outcomes under PEG or PEG plus SSAs for a minimum of 6 months. DATA EXTRACTION: Three reviewers screened eligible publications (7248), three others extracted the outcomes, and all assessed the risk of biases. DATA SYNTHESIS: Thirteen studies were included in the PEG and 5 in the PEG plus SSAs analysis (overall 550 subjects). PEG significantly decreased FPG [effect size (ES) -0.80 mmol/L (95% CI, -1.06 to -0.55); P = 0.000], HbA1c [ES -0.43% (95% CI, -0.56 to -0.31); P = 0.000], FPI [ES -5.31 mU/L (95% CI, -10.23 to -0.39); P = 0.034], and HOMA-I [ES -0.61 (95% CI, -1.17 to -0.04); P = 0.034]. Effects on FPG and FPI were not correlated to IGF-1 changes. The addition of PEG to SSAs mitigated the effects of SSAs on metabolism, producing an overall neutral effect. CONCLUSIONS: Independently of disease control, PEG in monotherapy or combined with SSAs seems to improve glucose metabolism, reducing FPG, HbA1c, FPI, and HOMA-I.