Combined therapy of somatostatin analogues with pegvisomant for the treatment of acromegaly: a meta-analysis of prospective studies

Background: Acromegaly is a rare, chronic and severe disease . Drug therapy including somatostatin analogues , dopamine receptor agonists and growth hormone receptor antagonists are commonly used to treat patients who do not responde to surgery. T he use of combination therapy with PEG and SAs has become more common over the last decade . We performed this study t o accurately evaluate the effect of combination therapy of somatostatin analogues (SAs) with pegvisomant (PEG) on acromegalic patients. Methods: PubMed, EMBASE, The Cochrane Library, and ClinicalTrials.gov were searched for relevant studies. Prospective clinical trials treating acromegaly with the co-administration of SAs and PEG were included. We performed a meta-analysis by using Stata 12.1 . Sensitivity analysis was conducted to explore heterogeneity. Results: Eight studies were included in this meta-analysis. The overall rate of serum insulin-like growth factor 1 (IGF-1) normalization was 75% (95% CI: 50%–93%; I 2 =93.60%). The combination therapy did not significantly change patients’ fasting plasma glucose (ES: 0.011 mmol*L -1 ; 95% CI: − 0.374 to 0.397 mmol*L -1 ; P=0.954) or glycosylated haemoglobin (ES: -0.106%; 95% CI: − 0.302% to 0.089%; P=0.285) while decreasing the fasting plasma insulin (ES: −21.487 pmol*L-1; 95% CI: −35.713 to -7.260 pmol*L-1; P=0.003). Elevation of liver enzyme levels was found in 14% (95% CI: 10% to 19%) of the patients. Conclusions: Combined therapy of SAs and PEG effectively normalized IGF-1 levels in most of the patients whose IGF-1 level was greater than the upper limit of normal after high dose SAs monotherapy. The combination therapy significantly decreased patients’ fasting plasma insulin. However, improved fasting plasma glucose or glycosylated haemoglobin was not found during the combination therapy. Moreover, elevated liver enzyme levels were observed in a small number of patients, which suggests a need for liver function monitoring. Trial registration We have our protocol registered in PROSPERO. (Registration number: CRD42019115549)