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Drug Res (Stuttg) 2022; 72(02): 86-93
DOI: 10.1055/a-1640-0226
Original Article

Regulations of Free Fatty Acids and Diabetic Parameters in Drug Naïve Subjects with Type 2 Diabetes Treated with Canagliflozin Monotherapy

Eiji Kutoh
1   Biomedical Center, Tokyo, Japan
2   Division of Diabetes and Endocrinology, Department of Internal Medicine, Gyoda General Hospital, Saitama, Japan
3   Division of Diabetes and Metabolism, Department of Internal Medicine, Higashitotsuka Memorial Hospital, Yokohama, Japan
,
Alexandra N. Kuto
1   Biomedical Center, Tokyo, Japan
,
Askuka Wada
2   Division of Diabetes and Endocrinology, Department of Internal Medicine, Gyoda General Hospital, Saitama, Japan
,
Rumi Kurihara
2   Division of Diabetes and Endocrinology, Department of Internal Medicine, Gyoda General Hospital, Saitama, Japan
,
Rina Kojima
2   Division of Diabetes and Endocrinology, Department of Internal Medicine, Gyoda General Hospital, Saitama, Japan
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Abstract

The objective of this study is to investigate the regulations of FFA with canagliflozin in relation to metabolic parameters. Drug naïve subjects with T2DM were administered 50–100 mg/day canagliflozin monotherapy (n=70) for 3 months. Significant correlations between the changes of (Δ) FFA and Δadipo-IR (R=0.496), but no correlations between ΔFFA and ΔHOMA-R were observed. The subjects were divided into three groups with similar numbers according to Δ FFA: group A: highest tertile: (ΔFFA=38.7%, n=23); group B: intermediate tertile: (ΔFFA=2%, n=23); group C: lowest tertile: (ΔFFA=−36%, n=24). Metabolic parameters were compared between group A and group C. At baseline, FFA was higher in group C than group A (p<0.002). Greater degrees of HbA1c reduction and increases of insulin were observed in group C than group A (both p<0.05). In group A, significant reductions of BMI (−2.6%) and HOMA-R (−30%) were seen. In group C, significant reductions of non-HDL-C (−6.2%), UA (−7.6%) or adipo-IR (−28.7%), and increases of HOMA-B (+85.6%) were observed. Taken together, 1) certain population treated with canagliflozin showed decreased FFA. 2) beta-cell function increased while atherogenic cholesterol, UA and adipo-IR decreased in those with reduced FFA. Better glycemic efficacies were seen in these populations. 3) body weight and whole body insulin resistance (HOMA-R) significantly decreased in those with elevated FFA. 4) FFA is linked to adipose insulin resistance (adipo-IR), while it does not appear to impact whole body insulin resistance (HOMA-R).

Key words

canagliflozin/SGLT-2 inhibitor - free fatty acid - insulin resistance - beta-cell function


Publication History

Received: 17 July 2021

Accepted: 29 August 2021

Article published online:
02 November 2021

© 2021. Thieme. All rights reserved.

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