艾塞那肽注射液对血糖控制不佳的超重和肥胖2型糖尿病患者的临床研究

Clinical trial of exenatide injection in type 2 diabetes mellitus patients with overweight and obese and poorly controlled blood sugar

目的观察艾塞那肽注射液对血糖控制不佳的超重和肥胖2型糖尿病患者的临床疗效和安全性。方法 62例口服2种及以上降糖药物血糖控制不佳的2型糖尿病患者,随机分为试验组和对照组,各31例。对照组早晚餐前皮下注射门冬胰岛素30注射液,起始剂量由研究者根据临床经验判断;试验组给予艾塞那肽5μg,早晚餐前1 h皮下注射,能耐受治疗的1个月后改为10μg。2组均治疗16周。观察2组患者治疗前后腰围、体重、体重指数(BMI)、血压、空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(Hb A1c)、血脂和空腹胰岛素(FINS)、胰岛β细胞抵抗指数(HOMA-IR)等指标变化,并观察2组药物不良反应和低血糖等发生情况。结果治疗后,试验组FPG为(6.83±1.03)mmol·L^(-1),对照组为(6.61±0.97)mmol·L^(-1);试验组2 h PG为(9.02±1.17)mmol·L^(-1),对照组为(9.77±1.43)mmol·L^(-1);试验组Hb A1c为(7.24±1.23)%,对照组为(7.07±1.03)%,与治疗前比较,差异均有统计学意义(均P<0.05),组间差异均无统计学意义(均P>0.05)。试验组三酰甘油(TG)为(1.98±0.88)mmol·L^(-1),对照组为(2.33±1.25)mmol·L^(-1);试验组低密度脂蛋白胆固醇(LDL-C)为(3.37±0.71)mmol·L^(-1),对照组为(3.70±0.81)mmol·L^(-1),试验组HOMA-IR为4.23±2.64,对照组4.63±3.10,试验组与治疗前相比,差异无统计学意义(P>0.05)。试验组腰围为(94.53±6.73)cm,对照组为(99.87±7.43)cm;试验组体重为(76.70±8.20)kg,对照组为(84.90±8.10)kg;试验组BMI为(26.14±4.32)kg·m^(-2),对照组为(30.49±4.52)kg·m^(-2),差异均有统计学意义(均P<0.05)。治疗期间2组均无严重不良反应发生,试验组出现轻度胃肠道反应8例(25.81%),皮肤瘙痒1例(3.23%),低血糖事件1例(3.23%);对照组出现皮下注射处硬结1例(3.23%),低血糖事件8例(25.81%),差异有统计学意义(P<0.05)。结论艾塞那肽注射液治疗口服降糖药血糖控制不佳的超重和肥胖2型糖尿病患者疗效显著,可有效降低血糖,并有降低腰围、体重、血脂和改善胰岛素敏感性等降糖外优势,且低血糖发生风险低。

Objective To evaluate the clinical efficacy and safety of exenatide in overweight and obese type 2 diabetes mellitus patients with unsatisfactory glycemic controll - using oral antidiabetic drugs. Methods Sixty- two cases with overweight and obese type 2 diabetes and not responsive to more than two oral antidiabetic agents were randomly divided into control group （n = 31 cases ） and treatment group （n = 31 cases）. Patients in control group were treated with insulin aspart 30, the starting dose of insulin was deter- mined by the researchers according to clinical experience judgment. Patients in treatment group were given exenatide 5 μg by subcutaneous injection one hour before breakfast and dinner, then changed to 10 μg after one month if patients can tolerance. The treatment lasted for 16 weeks. The data of waistline, body weight, body mass index（ BMI）, blood pressure, fasting plasma glucose（ FPG）, 2 h postprandial plasma glucose（2 h PG）, hemoglobin Alc（ HbA1c） , lipids weight, fasting insulin（FINS） , homeostasis model assessment of insulin resistance index （ HOMA - IR）, the incidence of adverse drug reactions and hypoglycemia were recorded between the two groups. Results After treatment, the FPG, 2 h PG and HbA1c in treatment group were （6.83 ± 1.03 ） mmol·L^-1, （9.02 ± 1.17 ） mmol·L^-1, （7.24 ± 1.23 ） %. TheFPG, 2 h PG and HbA1c in control group were （6. 61 ±0.97）mmol·L^-1,（9.77 ± 1.43）mmol·L^-1, （7.07 ± 1.03 ） %, had significant difference with those before treatment（P 〈0. 05）. The TG, LDL - C and HOMA - IR in treatment group were （1.98 ±0. 88） mmol·L-1 , （3.37 ±0. 71） mmol·L^-1, 4.23 ±2.64, had no significant diffe- rence with those in control group, which were （2.33 ± 1.25） mmol·L^-1, （3.70 ±0. 81 ） mmol·L^-l, 4. 63 ±3.10 （P 〉0.05 ）. After treatment, the waistline, body weight and BMI in treatment group were （94.53 ± 6.73 ）cm, （76.70 ±8.20）kg, （26. 14 ±4.32）kg·m^-2, had significant difference with those in control group, which were （99. 87 ±7.43）cm, （84. 90 ± 8.10） kg, （30.49 ±4.52） kg·m^-2 （P 〈0. 05）. There were no serious adverse drug reactions in both groups during the treatment. There were 8 cases （25.81% ） of mild gastrointestinal reactions, 1 case （3.23%） of itchy skin and 1 case（3.23% ） of mild hypoglycemia in treatment group. While in control group, there were 1 case （3.23%） of subcutaneous induration and 8 cases （25.81% ） of mild hypoglycemia, the incidence had statistically significance beween two groups（P 〈 0. 05 ）. Conclusion Exenatide showed good clinical effect on blood glucose control by reducing waistline, body weight, blood lipid and improving the insulin resistance. Also, the incidence of mild hypoglycemia was lower in overweight and obese type 2 diabetes mellitus patients with unsatisfactory controlled blood sugar with oral antidiabetic drugs.