IMPACT OF OCTREOTIDE, A LONG-ACTING SOMATOSTATIN ANALOG, ON GLUCOSE-TOLERANCE AND INSULIN SENSITIVITY IN ACROMEGALY

OBJECTIVE We aimed to investigate the impact of a long-acting somatostatin analogue, octreotide, on glucose tolerance and on insulin sensitivity in acromegaly. DESIGN We performed a non-randomized controlled trial. PATIENTS Seven patients with active acromegaly were assessed before and during octreotide therapy given in a dose of 500-mu-g three times daily subcutaneously. MEASUREMENTS The effects of octreotide on carbohydrate metabolism were assessed by performing a glucose tolerance test and a euglycaemic hyperinsulinaemic clamp. These latter tests were undertaken 8 hours after the last dose, allowing GH and glucagon to return to pretreatment levels during the study. RESULTS Octreotide significantly reduced (P < 0.05) mean +/- SEM 12-h GH (from 42 +/- 13 to 10 +/- 3 mlU/l) and IGF-I (from 4.2 +/- 0.5 to 2.1 +/- 0.5 U/ml) concentrations. Glucose tolerance was normalized in four of five patients with impaired glucose tolerance without a significant change in mean insulin concentrations. The improvement in fasting and mean blood glucose during glucose tolerance testing was dependent on the pretherapy blood glucose concentrations (r = -0.95, P < 0.002). The glucose infusion rate during the hyperinsulinaemic (5 U/h) clamp was significantly increased (P < 0.05, 15.3 +/- 1.8 vs 24.2 +/- 5.4-mu-mol/kg min) following octreotide treatment. Insulin infusion during the glucose clamp completely suppressed hepatic glucose production during but not before octreotide treatment (7.9 +/- 2.4 vs 0.7 +/- 2.2-mu-mol/kg min, P = 0.02). Insulin-mediated stimulation of peripheral glucose uptake was unaffected by treatment. Mean GH and glucagon levels during both clamp studies were not significantly different. CONCLUSIONS Octreotide improves whole body insulin sensitivity by an increased ability of insulin to suppress hepatic glucose production without affecting the substantial impairment of peripheral insulin action. Octreotide has beneficial effects on carbohydrate metabolism in acromegalic patients with glucose intolerance.