Canagliflozin as an Initial Therapy in Drug-Naive 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-naive subjects with type 2 diabetes mellitus received canagliflozin 50-100 mg/day monotherapy. At 3 months, levels of glycemic and nonglycemic parameters were compared with those at baseline (n = 39). As a comparator, our previous data of baseline glycosylated hemoglobin (HbA(1c))-matched treatmentnaive 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 inHbA(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.