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Effects of Somatostatin Analogs on Glucose Homeostasis: A Metaanalysis of Acromegaly Studies

Department of Medical and Surgical Sciences (G.M., S.B., A.G.), University of Brescia, 25125 Brescia, Italy; Department of Oncology (I.F., V.T.), Istituto di Ricerche Farmacologiche "Mario Negri," 20156 Milan, Italy; Assistance Publique-Hôpitaux de Paris (P.C.), Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Service d’Endocrinologie et des Maladies de la Reproduction, Hôpital de Bicêtre, 94275 Le Kremlin Bicêtre, France; Institut National de la Santé et de la Recherche Médicale Unit 693, 94276 Le Kremlin-Bicêtre, France; and Faculté de Médecine, Université Paris-Sud 11, 94275 Le Kremlin-Bicêtre, France

Address all correspondence and requests for reprints to: Professor Andrea Giustina, Department of Medical and Surgical Sciences, University of Brescia, c/o Endocrinology Service, Montichiari Hospital, Via Ciotti 154, 25018 Montichiari, Italy. E-mail: a.giustina{at}libero.it.

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.

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