No abstract

No abstract

Objectives The aim of this study was to investigate the differential regulation of metabolic parameters between pioglitazone and canagliflozin in relation to their glycaemic efficacies. Methods Drug‐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. Results In 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.

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).

No abstract