AIMS/INTRODUCTION: We investigated the potential use of canagliflozin, in comparison with liraglutide, as an alternative to bolus insulin in patients with well-controlled type 2 diabetes mellitus receiving multiple daily insulin injection therapy. MATERIALS AND METHODS: In 40 patients, with glycated hemoglobin (HbA1c) levels <7.5% controlled by multiple daily insulin injection therapy, all bolus insulin was randomly switched to canagliflozin (100 mg/day) or liraglutide (0.3-0.9 mg/day) for 24 weeks. Basal insulin was continued with dose adjustment according to a predefined algorithm. The end-points were the change in the HbA1c level, glycemic variability assessed by continuous glucose monitoring, body mass index, insulin dose, quality of life (QOL) and safety assessments. Factors influencing the changes in QOL were also assessed using a simple regression analysis. RESULTS: The change in HbA1c from baseline was comparable between the treatments. Both treatments maintained the HbA1c level to the baseline levels with stable glucose variability and no severe hypoglycemia for 24 weeks, decreased total insulin dose, and significantly increased the QOL score. The change in QOL was significantly associated with injection frequency. CONCLUSIONS: For patients with well-controlled type 2 diabetes mellitus, under the support of basal insulin, complex insulin regimens can be simplified by replacing all bolus insulin with once-daily canagliflozin or liraglutide, which improves patients' QOL.