Many studies have recently shown that simple computer-solved indices, based on fasting glucose and insulin levels, closely mirror the euglycemic clamp technique in studying insulin resistance or pancreatic insulin secretion. Few data are at present available on the evaluation of these novel indices in acromegalic patients, known to be GH-dependent insulin-resistant subjects, in particular during medical treatment with somatostatin analogues. Indeed, these drugs are able to inhibit not only GH and IGF-I levels, but also insulin and glucagon pancreatic secretion, with contrasting effects on glucose metabolism. In this study, insulin resistance was evaluated by the homeostasis model assessment (HOMA-IR) and insulin sensitivity by quantitative insulin check index (QUICKI) in 27 normoglycemic acromegalic patients, before and after 6-month therapy with somatostatin analogues (lanreotide-SR 30-60 mg every 7-28 days in 15 and octreotide-LAR 20-30 mg every 28 days in 12). Thirty-five age- and sex-matched healthy subjects and 17 surgically treated acromegalic patients (5 cured and 12 not cured) were studied as control groups. Before medical treatment, HOMA-IR was higher in acromegalic patients than in healthy controls (4 +/- 3 vs 1.7 +/- 0.7, p < 0.05), while QUICKI was lower (0.33 +/- 0.04 vs 0.36 +/- 0.03, p < 0.05). During medical therapy, HOMA-IR decreased to 2.4 +/- 1.6 (p < 0.05) and became similar to that recorded in both healthy subjects and surgically treated patients. However, fasting glucose was increased and fasting insulin was decreased. QUICKI did not significantly change from basal values. No differences were observed between patients who normalized or not hormonal levels. The effects of the 2 drugs, though higher glucose levels were seen in patients treated with octreotide-LAR. In conclusion, this study demonstrates that medical treatment is able to improve insulin resistance, even if only successful surgery is able to completely normalize both HOMA-IR and QUICKI.