Somatostatin Analogs and Glucose Metabolism in Acromegaly: A Meta-Analysis of Prospective Interventional Studies

Introduction: Somatostatin analogs (SSAs) effectivelycontrol growth hormone secretion in first and second line treatmentof acromegaly. Their effect onglucose metabolism is still debated. Aim: to address the following questions: 1) Do SSAs affect fasting plasma glucose (FPG), fasting plasma insulin (FPI), glycosylated hemoglobin (HbA1c), glucose load (2h-OGTT), HOMA-I, HOMA-β, triglycerides (TGD), weight (W) or body mass index (BMI)? 2) Do lanreotide (LAN) and octreotide LAR (OCT) affect metabolism differently? 3)Does their effect depend on disease control? Methods: We performed a meta-analysis of prospective interventional trialstreating acromegaly with SSAs. Inclusion criteria: all studies reporting glyco-metabolic outcomes before and after SSAs with a minimum 6-month follow-up. Results: The inclusion criteria were met by 47 studies treating 1297 subjects (631 F). SSA treatment effectively lowered FPI (effect size [ES] -6.67 mU/L, 95%CI: -8.38 to -4.95mU/L; p<0.001), HOMA-I (ES -1.57, CI: -2.42 to -0.72; p<0.001), HOMA-β (ES -47.45, CI: -73.15 to -21.76; p<0.001) and TGD (ES -0.37 mmol/L, CI: -0.47 to -0.27 mmol/L; p<0.001). SSAs worsened 2h-OGTT (ES 0.59 mmol/L, CI: 0.05 to 1.13 mmol/L; p=0.032), but not FPG. A mild but significant increase in HbA1c (ES 0.12%, CI: 0.00to 0.25%; p=0.044) was found in OCT treated subjects. Conclusions: SSA treatment in acromegaly patients-while improving disease control- reduces insulin levels, increases after load glucose and, ultimately, increases HbA1c levels without affecting FPG. The findings suggest that clinicians treating acromegaly with SSAs should consider targeting post-prandial glucose.