• Eiji Kutoh, Alexandra N Kuto, Askuka Wada, Rumi Kurihara, and Rina Kojima.
• Biomedical Center, Tokyo, Japan.
• Int. J. Clin. Pract. 2021 Dec 1; 75 (12): e14914.

ObjectivesThe aim of this study was to investigate the differential regulation of metabolic parameters between pioglitazone and canagliflozin in relation to their glycaemic efficacies.MethodsDrug-naive subjects with T2DM received pioglitazone 15-30 mg/day or canagliflozin 50-100 mg/day monotherapy for 3 months. Those who had a ≥1% reduction in HbA1c were defined as responders and others who had a <1% reduction were defined as non-responders.ResultsIn the pioglitazone group, baseline BMI, FFA, HOMA-R or adipo-IR was significantly higher, and HDL-C was significantly lower in responders vs non-responders. In the canagliflozin group, baseline HbA1c or FBG was significantly higher, and HOMA-B or age was significantly lower in responders vs non-responders. In pioglitazone responders, significant decreases in HbA1c (from 10.75% to 8.31%), FBG (-29.7%), FFA (-37.7%), non-HDL-C (-13.4%), TG (-30.1%), HOMA-R (-35.6%) or adipo-IR (-38.7%), and increases in BMI (2.8%) or HDL-C (14.2%) were observed. In pioglitazone non-responders, none of the parameters were regulated. In canagliflozin responders, significant decreases in HbA1c (from 11.31% to 8.60%), FBG (32.1%), BMI (-2%) or HOMA-R (-33.8%), and increases in HOMA-B (50%) were observed. In canagliflozin non-responders, significant decreases in BMI (-2.4%), insulin (-21.8%) or HOMA-R (-33.6%) were observed.Conclusions(i) Glycaemic efficacy of pioglitazone is linked to body weight and atherogenic lipids while this is not the case with canagliflozin. (ii) Responders (or non-responders) to pioglitazone have some distinct features from non-responders (or responders) to canagliflozin. Collectively, a combination of pioglitazone and canagliflozin may compensate for each other's metabolic drawbacks or augment their advantages, thereby achieving overall improvements in the metabolic profiles and pathogenic defects of patients with T2DM.© 2021 John Wiley & Sons Ltd.

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