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

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).

Construction of fatty acid derivatives from rubber seed oil as α-glucosidase inhibitors based on rubber seed oil

“…At the same time, lots of seed oils have been found as an effective α-glucosidase inhibitor (Teng and Chen 2016 ). Kutoh et al reported the dietary omega-3 polyunsaturated fatty acids and their metabolic derivatives are potential drugs to prevent and treat diabetes (Kutoh et al 2021 ). Chen and Kang reported that the hexane extract from oriental melon seeds was an effective inhibitor for α-glucosidase with 35.30% inhibition rate at 2 mg/mL (Chen and Kang 2013 ).…”

Alogliptin: a unique DPP-4 inhibitor that regulates adipose tissue insulin resistance and atherogenic lipids

“…Unexpectedly, no correlations were noted between the changes of (D) adipo-IR and those of BMI or UA (Table IV). This is in contrast to other drugs that were shown to have links between these 3 parameters [14,15]. The physiological meaning of this unexpected observation remains to be further investigated.…”

“…Although some hypoglycemic drugs such as TZD (pioglitazone) or SGLT-2 inhibitors have been shown to regulate adipose tissues insulin resistance evaluated with adipo-IR [13,14,15], so far no DPP-4 inhibitor has been shown to regulate this parameter. Here we report that alogliptin, but not other drugs in this class (sitagliptin or teneligliptin) could down-regulate adipo-IR as well as some atherogenic lipids.…”

Experimental and Emerging Free Fatty Acid Receptor Agonists for the Treatment of Type 2 Diabetes

“…Groups with higher FFA had greater degrees of HbA1c reduction and increases in insulin, along with significant reductions of non-HDL-C, UA, and adipo-IR. Body mass and whole-body insulin resistance were also decreased in those with elevated FFA, though better glycemic control along with increased beta cell function and decreased atherogenic cholesterol were seen in those with reduced FFA [54].…”

“…Regulation of FFA in relation to metabolic factors were also investigated in drug naive subjects with T2DM who were treated with 50-100 mg of canagliflozin, a sodiumglucose transporter-2 agent, as monotherapy for 3 months [54]. Metabolic parameters were compared between groups with low FFA and high FFA.…”