The number of different medications available to treat patients with type 2 diabetes has increased dramatically over the past 2 decades. While metformin remains the mainstay of initial treatment, there is ongoing debate regarding the optimal choice when adding a second oral agent. In this issue of JAMA Internal Medicine, Xie et al1 examine the comparative effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors vs sulfonylureas on all-cause mortality among metformin users. This high-dimensional propensity score–matched cohort study observed patients enrolled in the Veterans Affairs health system who were receiving metformin and were prescribed either an SGLT2 inhibitor or sulfonylurea as a second medication. During the approximately 2 years of mean follow-up, SGLT2 inhibitor use was associated with a reduced risk of all-cause mortality compared with sulfonylureas, regardless of age, cardiovascular disease, or estimated glomerular filtration rate status (hazard ratio [HR], 0.81; 95% CI, 0.75-0.87).1 There was also a reduced risk of death with the combination of SGLT2 inhibitor and metformin compared with SGLT2 inhibitor use alone (HR, 0.70; 95% CI, 0.50-0.97).1 These findings reinforce the current American Diabetes Association guidelines,2 which recommend metformin as initial therapy followed by any one of a dipeptidyl peptidase-4 inhibitor, glucagonlike peptide-1 receptor agonist, thiazolidinedione, or SGLT2 inhibitor class medicine if a patient’s hemoglobin A1c level remains elevated.