Pasireotide (SOM230) Prevents Sulfonylurea-induced Hypoglycemia in Rats

Persistent hypoglycemia is a serious condition that is frequently reported in patients undergoing sulfonylurea treatment, often necessitating hospitalization in the event of overdose. Somatostatin is a regulatory hormone with a broad range of physiological actions that include the inhibition of insulin and glucagon secretion, predominantly via activation of the somatostatin receptor subtypes sstr₅ and sstr₂, respectively. Previous studies have demonstrated that octreotide, a potent somatostatin analogue with high affinity for sstr₂ and moderate affinity for sstr₅, significantly increases serum glucose levels and prevents recurrence of hypoglycemic episodes in patients with sulfonylurea-induced hypoglycemia. Pasireotide (SOM230) is a multireceptor-targeted somatostatin analogue with a 39-, 30- and 5-fold higher binding affinity for sstr₅, sstr₁ and sstr₃, respectively, and a slightly lower (0.4-fold) affinity for sstr₂ compared with octreotide. This study evaluated the effects of pasireotide and octreotide in rats with glyburide-induced hypoglycemia. In fasted rats, pasireotide (10 and 30 µg/kg) prevented glyburide-induced hypoglycemia in a dose-dependent manner for up to 6 h. Qualitatively similar results were observed in non-fasted rats. However, the antihypoglycemic effect of pasireotide was stronger in non-fasted rats, resulting in transient hyperglycemia. In contrast to pasireotide, octreotide 10 µg/kg did not prevent glyburide-induced hypoglycemia in fasted and non-fasted rats, while octreotide 30 µg/kg resulted in small but significant increases in blood glucose at 3 h post-dose only. These findings suggest that pasireotide could have a more potent effect than octreotide in the management of patients with severe hypoglycemia caused by hyperinsulinemia.