2344-PUB: Predictors of the Glucose-Lowering or Weight-Loss Effects of Ipragliflozin and Sitagliptin

Abstract

Sodium-glucose cotransporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor are widely used in Japan, but only a few studies have directly compared the effects of these two drugs. We have reported that ipragliflozin (Ipra) had beneficial effects on fat reduction, insulin resistance, and lipid metabolism, while sitagliptin (Sita) had beneficial effects on β-cell function in a randomized controlled study. In this subanalysis study, we screened for predictors of the glucose-lowering effects of Ipra and Sita, and the weight-loss effects of Ipra. The participants were 119 patients aged 20-75 years with type 2 diabetes, HbA1c ≥ 6.5%, and BMI ≥ 23 kg/m2, and were randomly assigned to 12 weeks of treatment with 50 mg of either Ipra or Sita. We analyzed the correlations between the change in glycated hemoglobin HbA1c (ΔHbA1c) or body weight (ΔBW) and multiple clinical variables at the baseline. In the Ipra group, the mean ΔHbA1c was -1.1% and ΔBW was -2.2 kg. There was no significant correlation between ΔHbA1c and ΔBW (ρ = 0.22, p = 0.095). ΔHbA1c had a significant positive correlation with age (ρ = 0.41, p = 0.001) and negative correlation with the HbA1c level (ρ = -0.68, p < 0.001), HOMA-IR (ρ = -0.36, p = 0.011), and ALT level (ρ = -0.34, p = 0.014), while ΔBW had a significant negative correlation with the total ketone concentration at the baseline (ρ = -0.31, p = 0.041). In the Sita group, the mean ΔHbA1c was -0.81%; no significant change in BW was seen. ΔHbA1c had a significant negative correlation with HbA1c level at the baseline (ρ = -0.42, p = 0.0016), but no significant correlation with other variables at the baseline. In conclusion, our results suggest that the glucose-lowering effects of Ipra were more prominent in younger patients with increased insulin resistance accompanied by fatty liver, while its weight-loss effects were more prominent in patients with high total ketone concentration at the baseline. Meanwhile, the glucose-lowering effects of Sita may be exhibited regardless of the patient pathology. Disclosure Y. Tsurutani: Research Support; Self; Astellas Pharma Inc. K. Nakai: None. J. Saito: None. M. Omura: None. T. Nishikawa: None.