Abstract:Objective To explore the effects of saxagliptin on glucolipid metabolism, islet β-cell function and intestinal flora in newly diagnosed patients with type 2 diabetes mellitus（T2DM）. Methods Twenty-three inpatients with newly diagnosed T2DM in the Second Affiliated Hospital of Nanjing Medical University from March 2018 to December 2019 were selected, and 11 healthy persons of physical examination were served as the control group at the same period. The T2DM patients were randomly divided into metformin group（n=11） and saxagliptin group（n=12） after being treated with insulin pump. Blood and fecal samples were collected before and after 12 weeks of treatment to observe the changes of blood glucose, blood lipid and islet β-cell function. Intestinal flora was analyzed and determined using 16S rRNA high-throughput sequencing technology. Results After 12 weeks of treatment, blood glucose levels, blood lipid and islet β-cell function were significantly improved compared with those before treatment(P＜0.05). The α diversity of bacterial flora in both groups decreased before treatment and increased after treatment (P＜0.05). In saxagliptin group, the abundances of Bacteroidetes and Romboutsia increased after treatment（P＜0.05）, and Firmicutes decreased by about one third. Compared with metformin group after treatment, the abundances of Phascolarctobacterium， Coprococcus， Lachnospiraceae_UCG-010 and Desulfovibrio decreased significantly in saxagliptin group（P＜0.05）. Heatmap analysis showed that the abundances of Phascolarctobacterium, Prevotella and Parabacteroides were negatively correlated with HOMA-IR（r=-0.727，-0.656，-0.636,P＜0.05）; Ruminococcus abundance was positively correlated with FPG and Prevotella abundance was positively correlated with HbA1c(r=0.670, 0.621, P＜0.05), while Akkermansia abundance was negatively correlated with FPG and Romboutsia abundance was negatively correlated with 2hPG(r=-0.711, -0.615, P＜0.05) . Conclusion Saxagliptin can regulate the intestinal flora, reduce the levels of blood glucose and blood lipids and improve the function of islet β-cell in T2DM patients.