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