Rodbard HW, Rosenstock J, Canani LH, et al. - In patients with type 2 diabetes (T2D) uncontrolled on metformin, researchers carried out this PIONEER 2 trial to compare the effectiveness and safety of glucagon-like peptide 1 (GLP-1) analog, oral semaglutide, and SGLT-2 inhibitor, empagliflozin. In a 52-week trial, study participants were randomized to once-daily open-label treatment with oral semaglutide 14 mg (n = 412) or empagliflozin 25 mg (n = 410). The trial was completed by 400 patients in the oral semaglutide group and 387 in the empagliflozin group. Gastrointestinal adverse events with oral semaglutide were more common. In patients with T2D uncontrolled on metformin, oral semaglutide was superior to empagliflozin in decreasing HbA_1c but not body weight at 26 weeks. At week 52, there was a significant decline in HbA_1c and body weight (trial product estimate) compared with empagliflozin. Within the established safety profile of GLP-1 receptor agonists, oral semaglutide was well tolerated.