Withdrawn: SGLT2 inhibitor ipragliflozin poses a low risk of hypoglycaemia owing to its blood glucose-dependent urinary glucose excretion mechanism in mice.

Abstract

Sodium-glucose cotransporter (SGLT) 2 inhibitors, which inhibit renal reabsorption of glucose and stimulate urinary glucose excretion, have been proposed as useful drugs for treating diabetes. This study examined the effects of the SGLT2 inhibitor ipragliflozin on blood glucose-dependent urinary glucose excretion in mice. To investigate the antihyperglycemic effects of ipragliflozin, several oral glucose tolerance tests (glucose load: 1-4 g/kg) were performed. Ipragliflozin significantly suppressed the increases in blood glucose levels concomitant with urinary glucose excretion. To investigate the risk of hypoglycemia, the effects of ipragliflozin were examined under fasting conditions in mice that prefasted for various time periods (0-24 h). Ipragliflozin significantly decreased blood glucose levels in mice that had prefasted for 0 or 6 h (non-hypoglycemic conditions), but not in mice that had prefasted for 12 h or more (hypoglycemic conditions). These ipragliflozin-induced hypoglycemic and urinary glucose excretion effects were well correlated with blood glucose levels. These results suggest that ipragliflozin-induced increases in urinary glucose excretion and accompanying hypoglycemic effects were caused by blood glucose-dependent mechanisms. Thus, ipragliflozin may be a useful antidiabetic agent that achieves ideal blood glucose control in diabetic patients with little risk of hypoglycemia.