A prospective observational study showed that decrease in body weight with canagliflozin is not linked with its glycemic efficacy and serum UA may amend beta-cell function during canagliflozin treatment.

Canagliflozin is one of the Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, a drug for type 2 diabetes mellitus (T2DM), having comparable glycemic and nonglycemic efficacies to other SGLT-2 inhibitors. It improves beta-cell function and insulin resistance by correcting glucotoxicity. Canagliflozin also imparts nonglycemic benefits, which include—weight reduction, diuretic action, renal protection, blood pressure control, and uric acid (UA) reduction.

But still, there is an ambiguity if its nonglycemic efficacies are associated with its glycemic efficacy. Therefore, a prospective, unblinded, observational study was conducted.

The study compared the effect of canagliflozin monotherapy on metabolic parameters among responders and non-responders (Grouped on the basis of new “A1c index” to assess glycemic efficacies). During the study, 50–100 mg/day canagliflozin was given for 3 months to drug-naïve patients with type 2 diabetes mellitus.

At 3 months, both the groups showed a comparable decrease in body mass index (BMI: −1.9% in responder vs. −1.8% with nonresponder) and homeostatic model assessment (HOMA)-R: −35.8% for responder vs. –31.5% for nonresponder). But differences were observed in other parameters.

Responders showed a significant increase of HOMA-B and a significant decrease in glycated hemoglobin (HbA1c), fasting blood glucose (FBG) and free fatty acid (FFA) and nonresponders showed a significant decrease of serum uric acid (UA) levels.

The result of the study showed that the responders with canagliflozin had lower BMI and beta-cell function.However, decrease in body weight with canagliflozin is not linked to its glycemic efficacy and decrease in FFA levels and improved beta-cell function denotes a potential mechanism of better glycemic efficacy of canagliflozin.

Moreover, it also suggested that serum UA may amend beta-cell function during canagliflozin treatment.

Source: Characterization of metabolic parameters in responders and nonresponders treated with canagliflozin monotherapy in drug-naive subjects with Type 2 diabetes. Kutoh E, et al. Indian J Endocr Metab. 2018;22:185-90.