Hyperglycemia Associated With Pasireotide: Results From a Mechanistic Study in Healthy Volunteers

Context: Pasireotide (SOM230) is a somatostatin analog with affinity for somatostatin receptor subtypes sst1–3 and sst5. Clinical trials have demonstrated the efficacy of pasireotide in treating Cushing's disease and acromegaly but have also shown adverse effects on glucose metabolism. Objective: The aim of the study was to evaluate the mechanism of pasireotide-associated hyperglycemia. Design: We conducted a randomized, single-center, open-label study. Subjects and Intervention: Forty-five healthy male volunteers were randomized to pasireotide 600 (n = 19), 900 (n = 19), or 1200 μg (n = 7) sc twice a day for 7 days. Randomization to 1200 μg was discontinued because of increased severity of gastrointestinal adverse events in this arm. An oral glucose tolerance test (OGTT), a hyperglycemic clamp test, and a hyperinsulinemic-euglycemic clamp test were performed on 3 consecutive days at baseline and treatment end. Main Outcome Measure: The effect of pasireotide on insulin secretion and hepatic/peripheral ins...