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

Abstract

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.

Fig. 1

Baseline-dependent reductions in glycosylated hemoglobin (HbA_1c) levels of canagliflozin. Simple regression analysis was performed between baseline HbA_1c and changes (Δ) in HbA_1c levels