Effects of somatostatin analogs on glucose homeostasis: a meta-analysis of acromegaly studies
Gherardo Mazziotti1, Irene Floriani2, Stefania Bonadonna1, Valter Torri2, Philippe Chanson3 & Andrea Giustina1
Objective: Somatostatin analogues (SSA) are widely used for the treatment of patients with neuroendocrine tumors. These drugs are able to influence glucose metabolism by an inhibitory effect of insulin secretion, but the clinical impact of this effect is uncertain. Most of the data on this topic have been obtained from studies including patients in acromegaly, one the major indication for SSA, which are limited in terms of numerosity and study duration. Therefore, we have carried out a meta-analysis on data from published, long-term trials in acromegaly in order to assess the clinical impact of SSA on glucose metabolism.
Methods: The outcomes analyzed were fasting plasma glucose concentration (FPG), fasting plasma insulin concentration (FPI), haemoglobin A(1c) (HbA1c) and plasma glucose during oral glucose tolerance test (OGTT). Eligibility criteria were: (1) duration of SSA treatment of at least 3 months; (2) available numerical data for at least one of the four biochemical outcomes investigated; (3) measurement of the outcomes before and after SSA treatment; (4) no selection of acromegalic patients for their responsivity to SSA. After revision, only 31 studies fulfilled eligibility criteria.
Results: SSA treatment was found to induce statistically significant decrease in FPI (effect size-0.45, 95% CI: −0.58; −0.32, P<0.001), without any significant change of FPG (effect size 0.04, 95% CI: −0.07; 0.15, P=0.52) and HbA1c (effect size 0.11, 95% CI: −0.02−0.23, P=0.09). Serum glucose values during OGTT were shown to significantly change during SSA treatment (effect size was 0.31, 95% CI: 0.17; 0.45, P<0.001) although with high inconsistency among trials.
Conclusions: Our data suggest that modifications of glucose homeostasis induced by SSA have an overall minor clinical impact in acromegaly. Although this does not mean that in selected patients a clinically significant deleterious effect may be observed, our findings suggest that SSA are drugs with a favourable risk/benefit ratio.