The efficacy and safety of once-weekly dulaglutide 0.75 mg (dulaglutide) compared with once-daily insulin glargine (glargine) in Japanese patients with type 2 diabetes were evaluated according to subgroups stratified by baseline glycated hemoglobin (HbA1c) (≤8.5% or >8.5%). This exploratory analysis of a randomized, open-label, phase 3 study included 361 patients. In both HbA1c subgroups (patients with baseline HbA1c ≤8.5% or >8.5%), a statistically significantly greater reduction in HbA1c was observed in dulaglutide-treated patients compared with glargine-treated patients after 26 weeks of treatment (HbA1c ≤8.5%: dulaglutide, -1.27%; glargine, -0.72%; HbA1c >8.5%: dulaglutide, -2.04%; glargine, -1.47%; p < 0.001 for both). Mean body weight was decreased from baseline in both subgroups of the dulaglutide group and increased in both subgroups of the glargine group; there were statistically significant differences between the treatment groups in both subgroups (p < 0.05 for both). In both subgroups, similar reductions in fasting blood glucose were observed for dulaglutide- and glargine-treated patients, and a greater reduction in postprandial blood glucose was observed for dulaglutide-treated patients compared with glargine-treated patients. Although dulaglutide increased gastrointestinal adverse events compared with glargine in both subgroups, all gastrointestinal events of diarrhea, nausea, constipation, and vomiting in dulaglutide-treated patients were mild in intensity and well tolerated. In both subgroups, there was a lower incidence of hypoglycemia with dulaglutide than with glargine. Dulaglutide demonstrated significantly greater HbA1c reduction compared with glargine, with an acceptable safety profile, regardless of baseline HbA1c.