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目的:探讨达格列净对新诊断2型糖尿病（T2DM）患者肠道菌群及胰岛β细胞功能的影响。方法:本研究为随机对照试验。选取2018年12月至2019年9月在江苏省盐城市亭湖区人民医院住院的52例新诊断T2DM患者作为研究对象，同时选取体检中心20名健康体检者作为正常对照组。T2DM患者住院后在专科护士的指导、糖尿病饮食的基础上予胰岛素强化治疗，血糖达标1周后停用胰岛素，采用随机数字表法分为达格列净组（剂量为10 mg，1次/d）和二甲双胍组（剂量为0.5~1.0 g，2次/d）。两组均用药12周。收集两组患者治疗前及治疗后的一般资料并检测临床指标，包括体重指数（BMI）、腰围、血尿酸、糖化血红蛋白（HbAn 1c）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、空腹血糖（FPG）、餐后2 h血糖（2hPG）、稳态模型评估胰岛素抵抗指数（HOMA-IR）、稳态模型评估β细胞功能指数（HOMA-β）等指标。同时收集两组患者治疗前及治疗后的粪便标本，通过16SrDNA测序检测粪便的菌群组成。组内各指标的比较采用配对样本n t检验，组间各指标的比较采用单因素方差分析或Kruskal-Wallis秩和检验。采用Spearman相关分析法分析肠道菌群与T2DM临床相关指标的相关性。n 结果:达格列净组26例，二甲双胍组26例。与二甲双胍组治疗后比较，达格列净组治疗后BMI、腰围、血尿酸、LDL-C、HOMA-IR水平下降，HDL-C、HOMA-β水平升高，差异均具有统计学意义（n P<0.05）。二甲双胍组、达格列净组和正常对照组分别有13、11和20例最终成功收集了粪便标本。二甲双胍组和达格列净组患者治疗后肠道菌群多样性显著增加（均n P<0.05），与二甲双胍组治疗后比较，达格列净组治疗后肠杆菌属、普氏梭杆菌属丰度水平明显降低，而普拉梭菌属和普雷沃菌属丰度明显升高，差异均具有统计学意义（n P<0.05）。Spearman相关分析结果显示，布劳特菌属、丹毒丝菌属丰度与FPG、2hPG、HbAn 1c水平均呈正相关（n r值分别为0.41、0.41、0.43，0.44、0.46、0.46；均n P<0.01），普拉梭菌属丰度与FPG、2hPG、HbAn 1c水平呈负相关（n r值分别为-0.36、-0.34，-0.46，均n P<0.01）。n 结论:在新诊断T2DM患者中，达格列净在降低体重、增加胰岛β细胞功能和改善胰岛素抵抗方面优于二甲双胍，两组治疗12周后都能改变肠道菌群组成结构，但达格列净和二甲双胍在改变特定菌群丰度水平方面有差异。“,”Objective:To study the effect of dapagliflozin on the composition of the gut microbiota and the function of β-cells in newly diagnosed type 2 diabetes mellitus (T2DM).Methods:A total of 52 newly diagnosed T2DM patients who were hospitalized in Yancheng Tinghu District People Hospital from December 2018 to September 2019 were enrolled, and 20 healthy people from the physical examination center were selected as the control group. In hospital, patients with T2DM were given intensive insulin therapy based on the guidance of specialist nurses and diabetic diet, which stopped insulin therapy one week after the blood glucose reached the target. T2DM patients were divided into two groups according to a random number table method: dapagliflozin group (dose of 10 mg, once per day) and metformin group (dose of 0.5 to 1.0 g, twice per day). The two groups were both treated for 12 weeks. The general data of the two groups of patients were collected and various indexes before and 12 weeks after treatment were recorded, including body mass index (BMI), waist circumference, uric acid, glycated hemoglobin An 1c (HbAn 1c), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), fasting blood glucose (FPG), 2 h postprandial blood glucose (2hPG), homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β), and so on. The feces samples of the two groups of the patients in both groups were collected before intervention and at 12 weeks after intervention. 16SrDNA sequencing to detect changes in gut microbiota composition were evaluated. The n t test was used for the comparison between the two groups. The comparison of each index between groups using an analysis of one-way analysis of variances or Kruskal-Wallis test. Spearman correlation analysis was used to analyze the correlation between differential gut microbiota and clinical parameters of T2DM.n Results:There were 26 cases in dapagliflozin group, 26 cases in metformin group. Compared to metformin group after 12 weeks treatment, the BMI, LDL-C, HOMA-IR level was significantly reduced, while the levels of HDL-C and HOMA-β were increased by dapagliflozin treatment, the differences were statistically significant (all n P<0.05). Fecal samples were successfully collected from 13 patients in metformin group, 11 patients in dagaglipin group and 20 patients in normal control group, respectively. The alpha diversity was significantly increased in metformin group and dapagliflozin group; for a comparison of two group, dapagliflozin treatment decreased the relative abundance ofn Enterobacteriaceae, n Flavonifractor and increased abundance of n Faecalibacterium and n Prevotellaceae compared to metformin group. Blautia positively correlated with the levels of FPG, 2hPG, and HbAn 1c (n r=0.41, 0.41, 0.43, respectively, all n P<0.01),n Faecalibacterium negatively correlated with the levels of FPG, 2hPG, and HbAn 1c (n r=-0.36, -0.34, -0.46, respectively, all n P<0.01),n Erysipelotrichaceae positively correlated with the levels of FPG, 2hPG, and HbAn 1c (n r=0.44, 0.46, 0.46, all n P<0.01).n Conclusions:In newly diagnosed T2DM patients, dapagliflozin group was superior to metformin group in reducing body weight, increasing pancreatic β-cell function, and improving insulin resistance. Gut microbiome composition was significantly altered in T2DM patients by both groups after 12 weeks treatment, however, there were differences in the composition structure and abundance level of gut microbiota after metformin and dapagliflozin treatments.