口服降糖药联合不同胰岛素类似物治疗血糖控制不佳2型糖尿病的临床研究

Clinical study of oral hypoglycemic agents combined with different insulin analogues for the treatment of type 2 diabetes mellitus with poor glycemic control

目的比较二甲双胍分别联合地特胰岛素、双相门冬胰岛素30治疗单纯口服降糖药血糖控制不佳2型糖尿病(T2DM)的临床疗效与安全性。方法选取2015年8月-2016年12月本院收治的112例口服降糖药血糖控制不佳的T2DM患者按随机数字分为A组(n=57)、B组(n=55),所有患者停服除二甲双胍(MET)外所有降糖药物,A组采用MET+地特胰岛素降糖方案,B组采用MET+门冬胰岛素30降糖方案,治疗12周后比较两组血糖指标、胰岛功能指标及药物不良反应。结果治疗期间,A、B组分别脱失2、1例;两组治疗12周后空腹血糖值(FPG)、餐后2 h血糖(2hPG)、糖化血红蛋白(HbA1c)均较治疗前显著下降,差异有统计学意义(P<0.05);两组FPG、HbA1c下降幅度绝对值差异无统计学意义(P>0.05),B组2hPG下降幅度绝对值显著高于A组[(5.16±1.33)vs.(4.61±1.24)mmol/L],差异有统计学意义(P<0.05);治疗12周后,B组FPG(53.7%vs. 47.3%)、2hPG(51.9%vs. 40.0%)、HbA1c(53.7%vs. 45.5%)达标比例均高于A组,但差异均无统计学意义(P>0.05);两组治疗12周后胰岛β细胞功能(HOMA-β)较治疗前显著升高,胰岛素抵抗指数(HOMA-IR)较治疗前显著下降,差异均有统计学意义(P<0.05);两组HOMA-β、HOMA-IR变化幅度绝对值差异均无统计学意义(P>0.05)。A、B两组治疗12周后体质指数(BMI)与治疗前差异均无统计学意义(P>0.05),两组治疗12周后BMI差异亦无统计学意义[(24.9±2.5)vs.(25.1±2.8)kg/m^2](P>0.05)。B组治疗期间症状性低血糖事件发生率、转氨酶升高、头痛、胃肠功能紊乱比例分别为18.52%、7.41%、1.85%、16.67%,与A组的10.91%、5.45%、5.45%、12.73%比较差异均无统计学意义(P>0.05)。结论对单纯口服降糖药血糖控制不佳的T2DM患者,采用MET分别联合地特胰岛素和双相门冬胰岛素30均能在无明显体重变异的基础上达到相似的降糖效果,双相门冬胰岛素30方案在降低餐后血糖方面略具优势。

Objective To compare clinical efficacy and safety of metformin(Met)combined with insulin detemir and biphasic insulin as part 30 in treatment of type 2 diabetes mellitus(T2DM)with poor glycemic control only with oral hypoglycemic drugs(OHD).Methods A total of 112 T2DM patients with poor glycemic control in August 2015 to December 2016 were enrolled and randomly divided into A(57 cases)and B(55 cases)group,all the patients stopped taking OHDs except for MET;group A was treated with MET+insulin detemir therapy,and group B was treated with MET+insulin aspart 30 therapy,both for 12 weeks.Blood glucose indexed,islet function and adverse drug reactions of the 2 groups were compared.Results During treatment,group A and group B lost 2 and 1 cases,respectively.There was no significant difference in the absolute values of fasting blood glucose(FPG)and glycosylated hemoglobin(HbA1c)between the two groups after 12 weeks of treatment(P>0.05).The absolute value of the decrease of blood glucose level(2 hPG)in group B was significantly higher than that in group A[(5.16±1.33)vs.(4.61±1.24)mmol/L](P<0.05).After 12 weeks of treatment,the proportion of FPG(53.7%vs.47.3%),2 hPG(51.9%vs.40.0%),and HbA1c(53.7%vs.45.5%)in group B was higher than those in group A,but the difference was not significant(P>0.05).There was no significant difference in the absolute changes of isletβ-cell function(HOMA-β)and islet resistance index(HOMA-IR)between the two groups after 12 weeks of treatment(P>0.05).There was no significant difference in body mass index(BMI)between the two groups after 12 weeks of treatment[(24.9±2.5)vs.(25.1±2.8)kg/m^2](P>0.05).The incidence of symptomatic hypoglycemia,transaminase elevation,headache and gastrointestinal dysfunction were higher in group B(18.52%,7.41%,1.85%and 16.67%)than in group A(10.91%,5.45%,5.45%and 12.73%).There was no significant difference between the two groups(P>0.05).Conclusions For T2DM with poor glycemic control purely through OHD,MET combined with insulin detemir or biphasic insulin aspart 30 both could achieve similar hypoglycemic efficacy without significant BMI variation.Biphasic insulin aspart 30 regimen was more superiority in postprandial glycemic control.