Aim and Methods: the randomized, double-blind, parallel-group, phase 3a PIONEER 3 study (NCT02607865) compared the efficacy and safety of oral semaglutide, a novel oral glucagon-like peptide-1 receptor agonist, with sitagliptin in patients with type 2 diabetes uncontrolled on metformin±sulfonylurea. Exploratory analyses of PIONEER 3 were conducted to assess the efficacy (HbA1c change from baseline and achievement of HbA1c<7.0%) of oral semaglutide (3, 7, or 14 mg) vs sitagliptin 100 mg at week 26 by baseline HbA1c and background oral antidiabetic drug(s) (OAD) subgroups. Results: in all treatment arms, HbA1c was reduced across all baseline HbA1c subgroups (HbA1c≤8.0, 8.0–≤9.0% and >9.0%) and in both OAD subgroups (metformin alone or metformin + sulfonylurea); reductions were greater with higher baseline HbA1c. HbA1c reductions were significantly greater with oral semaglutide 7 and 14 mg vs sitagliptin in all subgroups, except for 7 mg in the HbA1c≤8.0% subgroup (Figure). The odds of achieving HbA1c<7.0% were greater with oral semaglutide 7 and 14 mg vs sitagliptin in all subgroups, except for 7 mg in the HbA1c≤8.0% subgroup. The proportions of patients achieving HbA1c<7.0% with oral semaglutide 7 and 14 mg and sitagliptin, respectively, in each subgroup were as follows – baseline HbA1c≤8.0%: 60, 75 and 55%; 8.0–≤9.0%: 39, 53 and 16%; >9.0%: 32, 32 and 10%; metformin alone: 56, 68 and 41%; metformin + sulfonylurea: 35, 49 and 24%. Conclusion: oral semaglutide 7 and 14 mg significantly improved glycemic control vs sitagliptin across most HbA1c groups, and irrespective of background OAD use.