882-P: Effects of YG1699 and Sotagliflozin on Intestinal Glucose Absorption and GLP-1 in Mice

Le résumé fourni par la source

Background and Aims: YG1699, a dual inhibitor of SGLT1 and SGLT2, recently showed greater glucose reduction than dapagliflozin in patients with type 1 diabetes. This study examined whether YG1699 provides gastrointestinal SGLT1 inhibition. Materials and Methods: Male BALB/c mice (n=105) were randomly divided into five groups: vehicle, YG1699 at low (1mg/kg), medium (3mg/kg), and high doses (10mg/kg), and LX4211 (sotagliflozin) 10mg/kg by oral gavage. Animals received a 5g/kg glucose challenge 15 minutes after study drug. Animals were euthanized at various times to examine intestinal plasma GLP-1 and glucose content in small intestine, cecum, and colon. Differences between groups were evaluated by ANOVA. Results (See Table 1): Small intestinal glucose content 1 hour after glucose challenge increased in a dose-related fashion with YG1699 compared to vehicle (p<0.001 for each YG1699 group vs. vehicle). Similar results were found in cecum (p<0.05 for each YG1699 group vs. vehicle). Plasma GLP-1 and PYY concentrations at 1 hour were higher on YG1699 vs. vehicle. Intestinal glucose content in the sotagliflozin group was similar to vehicle and the plasma GLP-1 were only numerically increased in this group. Conclusion: YG1699 delays intestinal glucose absorption and induces an incretin response in BALB/c mice, indicating significant gastrointestinal SGLT1 inhibition. Disclosure J.Li: None. R.W.Xu: Consultant; Youngene Therapeutics. J.He: None. P.Lapuerta: Board Member; 4M Therapeutics, Consultant; Youngene Therapeutics, ViaCyte, Inc., Encuragen, Capsida, Provention Bio, Inc., Decibel Therapeutics, Crinetics, Next Phase Therapeutics.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.