INS and diabetes mellitus: In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study, intensive glucose control with insulin and gliclazide [46] significantly reduced the risk of ESRD by 65% (the number needed to treat was only 41), but increased the risk of severe hypoglycaemia, which was associated with an increase in cardiovascular death [47].