First, we created disease subgroups in which second-generation diabetes drugs had shown early evidence of advantage: chronic kidney disease for DPP-4 inhbitors,22 ischemic heart disease for GLP-1 receptor agonists,23 and heart failure for SGLT-2 inhibitors.8 We then estimated the RR of initiation with each second-generation drug in each disease subgroup (Table 2). This evidence concerns the gene SLC5A2 and heart failure.