Management of hyperglycemia during pasireotide treatment

Introduction: The novel multireceptor-targeted somatostatin analogue pasireotide (SOM230) is a promising second-line therapy in treatment-resistant Cushing's disease. Pasireotide has a broad somatostatin-receptor binding profile with high binding affinity for somatostatin-receptor subtype 5, which is primarily expressed by pituitary corticotroph adenomas. Treatment with pasireotide reduces urinary free cortisol and serum cortisol levels and results in improvement in symptoms of Cushing's disease like decrease in body weight, blood pressure and LDL levels. However, pasireotide related hyperglycemia is a frequent complication. Data from studies involving healthy volunteers suggest that pasireotide-induced hyperglycemia is a result of decreased insulin and incretin secretion, most likely attributable to its interaction with somatostatin receptors in the gut, whereas insulin sensitivity is unaffected. Hyperglycemia occurs independent of dosage and despite decline in cortisol levels during pasireotide treatment. Methods: Here, we report on three patients with pasireotide-induced hyperglycemia: All patients had already undergone transsphenoidal surgery and radiation therapy, before starting treatment with pasireotide 900 µg twice daily. Results: In all patients, improvement of cortisol levels could be observed after starting pasireotide treatment. HbA1c increased in all patients, with one patient showing a maximum of 8.5%. Additional treatment with oral anti-diabetic drugs was necessary in two cases and out of these, one had to be put on insulin therapy. Hyperglycemia in these two patients was also the reason for discontinuation of pasireotide treatment. Conclusion: Management of hyperglycemia is one of the major issues of treatment with pasireotide in Cushing's disease. Further investigation should find strategies to reduce the rate of pasireotide-induced hyperglycemia and evaluate the optimal management of affected patients.