The objective of this trial, the EMPA-REG H2H-SUTM trial, is to compare the effects of the SGLT2 inhibitor empagliflozin with the SU glimepiride given over the long term (4 years) as second-line therapy for T2DM in patients in whom metformin and diet/exercise has failed with respect to 1) glycemic control, 2) beta-cell function, 3) the CV risk factors: body weight, blood pressure and lipid levels, and 4) safety including prospectively adjudicated CV events and markers of renal function/damage. This evidence concerns the gene SLC5A2 and type 2 diabetes mellitus.