Link between body weight changes and metabolic parameters in drugs naïve subjects with type 2 diabetes treated with canagliflozin monotherapy

ABSTRACT

Objectives

The aim of this study is to investigate the correlations between the changes of body weight and metabolic parameters during canagliflozin treatment.

Methods

Drug naïve subjects with T2DM (n = 84) received canagliflozin monotherapy for 3 months. The subjects were divided into three groups with equal numbers of subjects (n = 28 each) according to the reductions of BMI levels; highest (group A), intermediate (group B), and lowest (group C) reductions. Changes of the metabolic parameters were compared between group A and group C. These two groups acted as a control of each other.

Results

Significant reductions of BMI levels (−4.1%, p < 0.00001) were observed in group A, while, surprisingly, significant increases (+1.5%, p < 0.00001) were seen in group C. In these two groups, similar reductions of HbA1c, FBG, or HOMA-R, and increases of HOMA-B levels were observed. Significant reductions of TG levels (−18.6%) were seen only in group A. At baseline, HbA1c levels were significantly lower in group A versus group C (p < 0.03). In group A, significant correlations between the changes of BMI and those of HbA1c (R = 0.496) were seen. By contrast, in group C, significant negative correlations were observed between these parameters (R = −0.463).

Conclusions

These results suggest that certain populations treated with canagliflozin gained weight, though similar glycemic and beta-cell/insulin sensitivity enhancing properties were observed in comparison to those with efficient weight reductions. Those who lost more weight had better glycemic efficacy in group A. By contrast, those who gained more weight had better glycemic efficacy in group C. Distinct glucose-lowering mechanisms might be operating between these two groups. Involvement of some factors including glucagons and free fatty acids is hypothesized.

KEYWORDS:

• Body weight change
• SGLT-2 inhibitor
• canagliflozin
• glucagons
• free fatty acid

Acknowledgments

The author thanks Drs. Kenji Kawashima, Kenichi Yamazaki, Hiromichi Suzuki, Daisuke Kurokawa, and Naoki Hamano for discussions and useful advice.

Declaration of interest

The authors declare that no conflict of interests exists regarding this manuscript.

Financial disclosures

The contents of the paper and the opinions expressed within are those of the authors, and it was the decision of the authors to submit the manuscript for publication.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.