利拉鲁肽、双歧杆菌三联活菌胶囊用于胰岛素+口服药疗效不佳的肥胖2型糖尿病患者的疗效观察OACSTPCD

OBJECTIVE:To probe into the efficacy and mechanism of liraglutide+Bifidobacterium triple viable capsules in the treatment of obese type 2 diabetes mellitus(T2DM)with poor efficacy of insulin+oral drugs based on blood glucose excursion,adipocyte inflammatory reaction and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway.METHODS:A total of 980 patients with obese T2DM with poor efficacy of insulin+oral medication admitted to our hospital from Jun.2022 to Jun.2023 were prospectively selected,which were divided into liraglutide group and combination group via single-blind method and random number table method,with 490 cases in each group.Both groups were given insulin+oral medication;on that basis,the liraglutide group received liraglutide,and combination group was given liraglutide+Bifidobacterium triple viable capsule.The fasting blood glucose,2 h postprandial blood glucose(2 hBG),glycated hemoglobin(HbA1c),body mass index(BMI),Insulin resistance index(HOMA-IR),C-peptide,glucose excursion,mean amplitude of glucose excursion(MAGE),area under the curve for blood glucose(AUCPG),adipocyte inflammatory response[secreted frizzled-related protein 5(sfrp5),Visfatin,Chemerin,tumor necrosis factor α(TNF-α),interleukin6(IL-6)],PI3K/Akt pathway[phosphorylated PI3K(P-PI3K),phosphorylated Akt(P-Akt)and nuclear factor-κB(NF-κB)]and safety were compared between two groups.RESULTS:After 4 and 12 weeks of treatment,the fasting blood glucose,2 hBG and HbA1c levels of the combination group were lower than those of the liraglutide group,the BMI and HOMA-IR of the combination group were lower than those of the liraglutide group,the C-peptide of the combination group was higher than that of the liraglutide group,the glucose excursion coefficient,amplitude peak of glucose excursion,MAGE and AUCPG>7.8 mmol/L of the combination group were lower than those of the liraglutide group,the sfrp5 of the combination group was higher than that of the liraglutide group,the Visfatin,Chemerin,TNF-α and IL-6 levels of the combination group were lower than those of the liraglutide group,the P-PI3K and P-Akt of the combination group were higher than those of the liraglutide group,the NF-κB of the combination group was lower than that of the liraglutide group,all of the above differences were statistically significant(P<0.05).The incidence of adverse drug reaction of the liraglutide group was 1.22%(6/490),compared with 0.61%(3/490)of the combination group,the difference was not statistically significant(P>0.05).CONCLUSIONS:The application of liraglutide+Bifidobacterium triple viable capsules on obese T2DM with poor efficacy of insulin+oral drugs is safe and reliable,which can play the dual role of glucose-reducing and weight-loss,improve patients'glucose excursion,insulin resistance and pancreatic β-cell function,inhibit adipocyte inflammatory response and regulate PI3K/Akt pathway,and might be used as a therapeutic option for obese T2DM patients with poor efficacy of insulin+oral drugs.