Investigation of efficacy and safety of low-dose sodium glucose transporter 2 inhibitors and differences between two agents, canagliflozin and ipragliflozin, in patients with type 2 diabetes mellitus.

Sodium glucose transporter 2 inhibitors (SGLT2is), new antidiabetic agents, were reported to improve not only glycemic parameters but also metabolic and circulatory parameters. Whereas, several adverse events caused by SGLT2is were also reported. We aimed to investigate the changes of glycemic, metabolic, and circulatory parameters as well as safety with low-dose administration of two SGLT2is, canagliflozin and ipragliflozin, and also the difference between the two agents. 25 individuals with type-2 diabetes mellitus (T2DM) were recruited and administered with low-dose SGLT2is, canagliflozin (n = 10, 50 mg/day) and ipragliflozin (n = 15, 25 mg/day). We examined glycemic, metabolic, and circulatory parameters at baseline and 24 weeks after administration. All patients completed the study without complications. Compared with baseline, levels of glycated hemoglobin, fasting plasma glucose, and homeostasis model assessment of ß-cell function improved significantly at 24 weeks after administration (p < 0.05). Levels of body weight, low-density lipoproteincholesterol, aspartate transaminase, γ-glutamyl transferase, and urinary excretion of albumin also improved significantly (p < 0.05). Moreover, systolic/diastolic blood pressure and levels of brain natriuretic peptide improved significantly (p < 0.05). The comparison of improvement ratio (values of improvement/values of basement) of each agent revealed that there was a significant difference between low-dose canagliflozin and low-dose ipragliflozin for brain natriuretic peptide (0.4404 vs. 0.0970, p = 0.0275). Hence, low-dose SGLT2is could be useful for patients of T2DM not only for hyperglycemia but also for metabolic and circulatory disorders without eliciting adverse events. In addition, with regard to the efficacy upon cardiovascular function, canagliflozin could be more suitable than ipragliflozin.