: The 'glutides,' which stimulate the glucagon-like peptide 1 (GLP-1) receptor to stimulate insulin secretion, are used in the treatment of type 2 diabetes. Semaglutide is the first glutide to be developed in an oral form. The PIONEER series of clinical trials (Peptide Innovation for Early Diabetes Treatment) were undertaken to establish a clinical role for oral semaglutide.: This evaluation is of PIONEER 6 in a non-inferiority phase 3a trial. In PIONEER 6, the primary outcome was the time from randomization to first occurrence of a major adverse cardiovascular event and this was non-inferior with oral semaglutide, compared to placebo.: In my opinion, there are several reasons why once-daily oral semaglutide may not replace once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes. Most importantly, subcutaneous semaglutide has already been shown to be superior to placebo in reducing cardiovascular risk, whereas the study of this with oral semaglutide will not be completed until 2024. Secondly, it is debatable whether subjects will find the daily protocol for taking oral semaglutide more convenient than that for the weekly subcutaneous formulation.