Luseogliflozin Additively Enhances the Glucose-Lowering Effect of an Incretin Modulator in a High-Carbohydrate Diet

Background and objectives Sodium/glucose co-transporter 2 inhibitors (SGLT2i) have been shown to have a glucose-lowering effect related to carbohydrate intake. It has also been reported that the combined effect of incretin modulators and SGLT2i is useful in improving blood glucose and reducing blood glucose variability. However, there have been no reports examining the effects of these two drugs together and while considering carbohydrate intake in an outpatient setting. In the present study, Hi-Speed Food Analysis was used to assess the exact intake of carbohydrates, and the glucose-lowering effects of luseogliflozin, an SGLT2i, and incretin modulators were examined under high- and low-carbohydrate intakes. Methods Thirty-five enrolled diabetic patients continued their regular medications for one week. All patients took luseogliflozin in the second week for seven days. During the two weeks, ingested carbohydrates were accurately calculated by Hi-Speed Food Analysis. The glucose-lowering effect of luseogliflozin with and without incretin modulators was checked according to the amount of ingested carbohydrates. A general linear model (GLM) was used to analyze the effect of luseogliflozin with or without an incretin modulator, with carbohydrate intake as a confounding factor. Results Luseogliflozin had an additive effect in patients who had taken the incretin modulator. There was a significant decrease in the time above range (TAR) with glucose above 140 mg/dL as expressed as TAR(min140), and this effect was affected by carbohydrate intake. Conclusions The glucose-lowering effect of luseogliflozin was enhanced with high-carbohydrate intake more than with low-carbohydrate intake. In this study, the observed number was small; however, combined treatment with an incretin modulator and luseogliflozin had an additive effect in high- versus low-carbohydrate intake, indicating the possible effectiveness of the combined therapy.