INS and lactic acidosis: The first controlled trial in diabetes was the University Group Diabetes Program (UGDP) (1960–1970), which compared the effects of diet alone, tolbutamide, fixed-dose insulin, variable-dose insulin, and phenformin in reducing large vessel disease or death in recently diagnosed type 2 diabetes patients.50 The study resulted in a series of controversies as excessive deaths were reported in the phenformin group because of lactic acidosis and in the tolbutamide group because of cardiovascular events.