Glucagon-like peptide-1 receptor agonists (GLP-1RA) are effective agents for achieving glycemic control. Oral semaglutide is the first oral formulation of a GLP-1RA to be approved in the USA. This agent may lead to earlier initiation of GLP-1RA therapy in the type 2 diabetes continuum of care, and represents a valuable treatment option for patients with a preference for oral therapy. The efficacy and safety of oral semaglutide was assessed in the PIONEER clinical trial program, which included 9543 patients (1293 Japanese). The program included 10 trials, two of which were conducted specifically in Japan. Across the whole program, oral semaglutide was shown to be effective in helping patients achieve glycemic control and reducing body weight. The highest approved dose of oral semaglutide (14 mg) reduced glycated hemoglobin significantly more than placebo, empagliflozin, dulaglutide, and sitagliptin, and was non-inferior to liraglutide. Superior reductions in body weight were also observed with oral semaglutide 14 mg compared with placebo, sitagliptin, and liraglutide, and similar body weight reductions were seen vs. empagliflozin. In all the PIONEER trials, oral semaglutide was well tolerated; there were no unexpected safety concerns and the safety profile was consistent with other GLP-1RAs. Oral semaglutide also demonstrated a favorable cardiovascular safety profile, and significant reductions in cardiovascular death and all-cause mortality vs. placebo in the PIONEER 6 trial. Oral semaglutide, therefore, represents an effective treatment option, that may lead to earlier initiation of GLP-1RA therapy in the diabetes treatment landscape.