New mechanism for sulfonylureas

Japanese researchers have uncovered a second mechanism by which sulfonylureas stimulate insulin production.¹ Exploiting the new mechanism to develop sulfonylurea analogs could produce compounds that do not exhaust the insulin-producing capacity of pancreatic β cells. The question is whether such compounds could generate better results than marketed incretin analogs and receptor agonists that work upstream in the pathway.

Sulfonylureas are the oldest class of oral diabetic drugs. The first sulfonylurea was approved in the U.S. in 1954. The drugs block the ATP potassium channel (K_ATP) on pancreatic β cells, thus causing membrane depolarization and the release of insulin. In healthy patients, higher glucose levels are sufficient to alter the membrane potential of pancreatic β cells and stimulate insulin secretion, but the process is impaired in type 2 diabetics...