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

Context: Somatostatin analogs (SSAs) effectively control growth hormone secretion in first-and second-line treatment of acromegaly. Their effect on glucose metabolism is still debated. Objective: To address the following questions: (1) Do SSAs affect fasting plasma glucose (FPG), fasting plasma insulin, glycosylated hemoglobin (HbA1c), glucose load (glucose levels after 2-hour oral glucose tolerance test), homeostatic model assessment of insulin resistance (HOMA-I), homeostatic model assessment of pancreatic beta-cell function (HOMA-beta), triglycerides, weight, or body mass index? (2) Do lanreotide and octreotide affect metabolism differently? (3) Does their effect depend on disease control? Design: We performed a meta-analysis of prospective interventional trials treating acromegaly with SSAs. Inclusion criteria: all studies reporting glycometabolic 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 females). SSA treatment effectively lowered fasting plasma insulin [effect size (ES), -6.67 mU/L; 95% confidence interval (CI), -8.38 to -4.95 mU/L; P < 0.001], HOMA-I (ES, -1.57; CI, -2.42 to -0.72; P < 0.001), HOMA-b (ES, -47.45; CI, -73.15 to -21.76; P < 0.001), and triglycerides (ES, -0.37 mmol/L; CI, -0.47 to -0.27 mmol/L; P < 0.001). SSAs worsened glucose levels after a 2-hour oral glucose tolerance test (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, 0.00% to 0.25%; P = 0.044) was found in subjects treated with octreotide. 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 postprandial glucose.