Canagliflozin as an Initial Therapy in Drug-Naïve Subjects with Type 2 Diabetes Mellitus: A Potential Involvement of Atherogenic Lipids in its Glycemic Efficacy

BACKGROUND AND OBJECTIVES: The aim of this study is to investigate canagliflozin as an initial therapy in type 2 diabetes mellitus and to explore the effects on metabolic parameters in relation to effects on glycemic control. SUBJECTS AND METHODS: Treatment-naïve subjects with type 2 diabetes mellitus received canagliflozin 50–100 mg/day monotherapy. At 3 months, levels of glycemic and non-glycemic parameters were compared with those at baseline (n = 39). As a comparator, our previous data of baseline glycosylated hemoglobin (HbA(1c))-matched treatment-naïve subjects with ipragliflozin 25–50 mg monotherapy (n = 27) were employed. RESULTS: Significant reductions in HbA(1c) (from 9.96 to 8.33%), fasting blood glucose (−23.9%), homeostasis model assessment-R (HOMA-R, −33.5%), body mass index (−1.8%), and uric acid (UA, −5.2%) levels and significant increases in homeostasis model assessment-B (HOMA-B, 30.1%) levels were observed. Approximately one third of the subjects experienced certain adverse events. Similar results were obtained with ipragliflozin. Baseline levels of HbA(1c), triglycerides, non-high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) were chosen as significant contributing factors for the changes in HbA(1c) levels with canagliflzoin, while only baseline HbA(1c) levels were selected as such a factor with ipragliflozin. Significant positive correlations between the changes in HbA(1c) and changes in non-HDL-C (R = 0.3954) or between changes in HbA(1c) and changes in LDL-C (R = 0.4317) were observed with canagliflozin. With ipragliflozin, no such correlations were noted. No correlations between the changes in HbA(1c) and changes in body mass index were seen with both drugs. CONCLUSIONS: These results suggest that (1) canagliflozin appears to offer clinically beneficial outcomes as an initial therapy in subjects with type 2 diabetes mellitus, although with certain adverse events. (2) Atherogenic cholesterols including non-HDL-C and LDL-C could be involved in the glycemic efficacy of canagliflozin. This was not the case with ipragliflozin. (3) Unexpectedly, weight reductions with canagliflozin are not associated with its glycemic efficacy.