Background and Aims: this exploratory subgroup analysis of the PIONEER programme evaluated the effect of baseline HbA1c on overall HbA1c and bodyweight reductions achieved during each trial. Materials and Methods: data from patients who participated in PIONEER 1–5, 7 and 8 (n=5657) were grouped by trial and according to baseline HbA1c (≤8.0%, >8.0–≤9.0% and >9.0%). In the PIONEER trials, patients received either once daily treatment with oral semaglutide (3, 7 or 14 mg, or flexibly dosed) or a comparator (placebo, empagliflozin 25 mg, sitagliptin 100 mg or liraglutide 1.8 mg). Endpoints were change from baseline in HbA1c and bodyweight at week 26 (week 52 in PIONEER 7). Results: reductions from baseline in HbA1c and bodyweight were greater with increasing oral semaglutide dose. HbA1c reductions were also greater with higher baseline HbA1c, but there was no consistent relationship between change in bodyweight and baseline HbA1c. Reductions in HbA1c were greater with oral semaglutide 7 mg and 14 mg versus placebo and versus active comparator in all subgroups (Table). Significant interactions by baseline HbA1c were observed for oral semaglutide vs comparator in PIONEER 3 (14 mg), PIONEER 4 (14 mg vs placebo), and PIONEER 8 (7 and 14 mg). Conclusions: oral semaglutide showed improved glycaemic control across baseline HbA1c subgroups in the PIONEER trials, with greater reductions in HbA1c with oral semaglutide 7 and 14 mg versus all comparators in all subgroups. Reductions in HbA1c were greater with higher oral semaglutide dose and higher baseline HbA1c.