ADVANCE to ADVANCE-ON: Unfolding the "Legacy Story" in Diabetes

Type 2 diabetes mellitus (T2DM) is a progressive disease. The importance of early intensive glucose lowering in preventing vascular complications in diabetes is well established. Sulfonylureas (SU) is recommended by most guidelines and widely used for the management of T2DM. However, there has been ambiguity around the long-term benefits with regard to microvascular and macrovascular outcomes with SUs. The United Kingdom Prospective Diabetes Study (UKPDS) provided evidence of sustained cardiovascular (CV) and microvascular benefits of previous intensive glycemic control with SUs or insulin in T2DM patients. The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release (MR) Controlled Evaluation (ADVANCE) trial, another landmark study in T2DM patients and its posttrial observational follow-up (FU) study [ADVANCE-Observational Study (ADVANCE-ON)] together provide definite evidence for sustained renal benefits of gliclazide MR based intensive glucose control initiated early during the course of diabetes. These effects, however, may be specific to gliclazide. Evidence from other studies and reviews also suggests that gliclazide MR may hold a distinct place among currently available SUs and reinforce its utility in diabetes management.