Background: Somatostatin analogs (SSA) may influence glucose metabolism, but the clinical relevance of this effect is uncertain because trials performed so far are limited in terms of number of patients and heterogeneity for length and type of follow-up. Purpose: The purpose of the study was to assess, via the metaanalysis of acromegaly studies, the clinical impact of SSA on glucose metabolism. The outcomes analyzed were fasting plasma glucose, fasting plasma insulin, hemoglobin A(1c), and plasma glucose concentrations during oral glucose tolerance test. Study Selection: Eligibility criteria were: 1) duration of SSA treatment of at least 3 wk; 2) available numerical data for at least one of the four biochemical outcomes investigated; 3) measurement of the outcomes before and after SSA treatment; and 4) no selection of acromegalic patients for their responsivity to SSA. After revision, only 31 studies fulfilled eligibility criteria and were therefore selected for data extraction and analysis. Data Synthesis: SSA treatment was found to induce statistically significant decrease in fasting plasma insulin effect size −0.45, 95% confidence interval (CI) from −0.58 to −0.32, P < 0.001, without any significant change of fasting plasma glucose (effect size +0.04, 95% CI from −0.07 to +0.15, P = 0.52) and hemoglobin A(1c) (effect size +0.11, 95% CI from −0.02 to +0.23, P = 0.09). Serum glucose values during the oral glucose tolerance test were shown to significantly change during SSA treatment (effect size +0.31, 95% CI from +0.17 to +0.45, P < 0.001), although with high inconsistency among trials. Conclusions: Our data suggest that modifications of glucose homeostasis induced by SSA may have an overall minor clinical impact in acromegaly. A meta-analysis suggests that changes in examined parameters of glucose homeostasis, induced by somatostatin analog therapy in acromegaly, may have an overall minor clinical impact.