Objective To study the efficacy and safety of glargine insulin combined with glimepiride therapy in type 2 diabetes mellitus(T2DM).Methods According to the random number table,100 T2DM patients with unsatisfactory efficacy of oral hypoglycemic agents were randomly divided into treament group and control group, 50 cases in each group.Then,the treatment group was dealed with glargine insulin and glimepiride,the control group were treated with insulin glargine for our treatment protocol.12 weeks after treament,the fasting blood glucose(FPG), 2 hours blood glucose(2hPG),body mass index(BMI),glycosylated hemoglobin(HbA1c),islet β-cell function index(HOMA -β),insulin resistance index(Homa -IR),insulin dosage(INS),time requirds,weight gain and so on were observed.Meanwhile,The occurrence condition of hypoglycemia was also observed.Results In control groups, the post -treatment indexes of FPG,2hPG,HbAlc,HOMA -βand HOMA -IR[(5.7 ±0.8)mmol/L,(8.6 ± 2.5)mmol/L,(6.5 ±0.7)%,(40.35 ±3.12),(2.68 ±1.41 )]were much better than those in pre -treatment [(11.7 ±1.6)mmol/L,(15.1 ±6.1 )mmol/L,(9.2 ±1.1 )%,(19.01 ±2.79),(3.42 ±1.47)](t =23.717, 6.971,14.642,36.052,2.568,P <0.01 or 0.05 for both).In the treatment group,the post -treatment indexes of FPG,2hPG,HbAlc,HOMA -β,HOMA -IR[(5.6 ±0.7)mmol/L,(7.3 ±2.3)mmol/L,(6.3 ±1.0)%,(54.18 ± 3.23),(2.12 ±1.26 )]improved obviously than those in pre -treatment [(11.8 ±1.7 )mmol/L,(15.8 ± 5.2)mmol/L,(9.3 ±1.2)%,(18.71 ±3.12),(3.36 ±1.56)](t =23.846,10.570,13.580,55.849,4.372,P <0.01 for both).After treatment,the indexes of 2hPG,HOMA -β,HOMA -IR,insulin dose,time requirds and ampli-tude of weight gain[(7.3 ±2.3)mmol/L,(54.18 ±3.23),(2.12 ±1.26),(18.06 ±1.43)U /d,(10.1 ±2.4)d, (1.1 ±0.4kg)]etc in the treatment group were significantly ameliorated than those in the control group[(8.6 ± 2.5)mmol/L,(40.35 ±3.12),(2.68 ±1.41 ),(22.46 ±1.77)U /d,(13.2 ±2.6)d,(2.1 ±0.6)kg](t =23.717,6.971,14.642,36.052,2.568,P <0.01 or 0.05 for both).Hypoglycemia events of treatment group were 4 cases(8.0%)and the same in the control group were 13 cases(26.0%),there were statistical significance between the two groups(χ2 =5.535,P <0.05).Conclusion Treatment of glargine insulin combined with glimepiride can improve blood glucose level of T2DM patients,recover their islet β-cell function,relieve the IR,shorten the time requirds,as well as reduce the insulin dosage,range of weight gain and rate of hypoglycemia events.Hence,treatment protocol of glargine insulin combined with glimepiride is an effective clinical treatment for newly diagnosed T2DMpatients.