Characterization of Metabolic Parameters in Responders and Nonresponders Treated with Canagliflozin Monotherapy in Drug-naive Subjects with Type 2 Diabetes.

Objectives: The aim of this project is to compare the effect of canagliflozin monotherapy on metabolic parameters between responders and nonresponders with this drug. This study is a prospective, unblinded, observational study.

Subjects and Methods: Drug-naïve patients with type 2 diabetes mellitus received only 50-100 mg/day canagliflozin for 3 months ( n = 39). They were divided into two groups according to the novel "A1c index" to assess glycemic efficacies; responders ( n = 24) and nonresponders ( n = 15).

Results: At baseline, glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) were significantly higher and homeostatic model assessment (HOMA)-B and body mass index (BMI) were significantly lower in responders. In both groups, similar, significant reductions of BMI (-1.9% with responder and -1.8% with nonresponder) and HOMA-R (-35.8% for responder and -31.5% for nonresponder) were observed. However, differences were seen with other parameters as follows: 1) responders: significant reductions of HbA1c (10.95%-8.44%), FBG (-29.6%) or free fatty acid (FFA) (-16.2%), and significant increases of HOMA-B (79.7%) were observed. 2) Nonresponders: significant reductions of serum uric acid (UA) (-8.6%) levels were seen. Significant correlations were observed between the baseline levels of serum UA and those of HOMA-B ( R = 0.7259). However, this link became uncorrelated with the treatment with canagliflozin.

Conclusions: These results suggest that (1) responders with canagliflozin have lower BMI and beta-cell function. Reductions of body weight with canagliflozin were not associated with its glycemic efficacy, (2) reduced FFA levels and enhanced insulin sensitivity/beta-cell function could be a potential mechanism of good glycemic efficacy of canagliflozin, and (3) serum UA might be involved in modulating beta-cell function during canagliflozin treatment.