BI-10773, a sodium-glucose cotransporter 2 inhibitor for the potential oral treatment of type 2 diabetes mellitus.

摘要

BI-10773, being developed by Boehringer Ingelheim Corp, is a sodium-glucose cotransporter (SGLT)2 inhibitor for the oral treatment of type 2 diabetes mellitus (T2DM). Preclinical and clinical research has demonstrated that inhibition of SGLT2, the major pathway of renal glucose reabsorption, leads to increased urinary glucose excretion with concomitant reductions in fasting and postprandial plasma glucose levels, HbA1c levels and body mass. In phase I clinical trials in patients with T2DM, once-daily BI-10773 increased urinary glucose excretion resulting in dose-proportional reductions in fasting plasma glucose and mean daily glucose levels. BI-10773 was not associated with significant hypoglycemic episodes or other clinically important adverse events. Because of its mechanism of action, BI-10773 may be combined with other oral antidiabetic agents; indeed, the results of small trials suggested that coadministration of BI-10773 and metformin was safe and well tolerated. In animal studies, BI-10773 correlated with an increase in urinary volume and a reduction in body fat but not water content. This may represent an additional benefit of BI-10773 for the control of T2DM. At the time of publication, phase III clinical trials of BI-10773 were underway.