沙格列汀治疗单用二甲双胍治疗血糖控制不佳2型糖尿病患者疗效及安全性研究

沙格列汀治疗单用二甲双胍治疗血糖控制不佳2型糖尿病患者疗效

及安全性研究

目的探索沙格列汀對二甲双胍单药治疗血糖控制不佳2型糖尿病患者的安全性及有效性。方法选择2015年1月—2016年12月在该院内分泌科门诊及住院的糖尿病患者252例。将入选患者按照1：1的比例随机分配至沙格列汀组或者阿卡波糖组。两组患者均继续维持二甲双胍治疗，沙格列汀组患者在原降糖方案的基础上加用沙格列汀片5 mg/d，1次/d；阿卡波糖组加用阿卡波糖50 mg，3次/d。随访观察期24周。每4周随访1次。观察两组患者治疗前后的FPG、2 hPG、HbA1c的变化，并记录随访期间药物相关不良事件发生情况。比较上述指标的在两组的变化。结果①沙格列汀组与阿卡波糖组治疗后FPG、2 hPG较该组治疗前均有明显降低（P＜0.05）；与阿卡波糖组治疗后相比，沙格列汀组2 hPG 显著下降，差异有统计学意义（P＜0.05）；②干预24周后，沙格列汀组与阿卡波糖组各组HbAlc均有降低（P＜0.05）；与阿卡波糖组相比，沙格列汀组HbAlc 下降幅度更大（P＜0.05）；沙格列汀组HbA1c达标率为48.82%显著高于阿卡波糖组的35.20%，差异有统计学意义（P＜0.05）。③随访期间，阿卡波糖组胃肠道异常发生率高于沙格列汀组（16.80% vs 3.94%，P＜0.05）；沙格列汀组与阿卡波糖组的低血糖事件和因不良事件而终止者相比较差异无统计学意义（7.09% vs 6.40%、5.51% vs 4.80%，P>0.05）。结论对于二甲双胍单药治疗血糖不达标的2型糖尿病患者，加用沙格列汀可有效降糖，提高糖化血红蛋白达标率，且不增加低血糖和胃肠道反应风险。

标签：二肽基肽酶抑制剂；沙格列汀；2型糖尿病

[Abstracts] Objective This paper tries to assess the efficacy and safety of saxagliptin on patients with type 2 diabetes with inadequate glycemic control of metformin. Methods 252 patients with type 2 diabetes in this hospital from January 2015 to December 2016 were enrolled in the study. Patients were randomly assigned to the saxagliptin group and acarbose group at a 1：1 ratio. The patients in the two groups were treated with metformin，and the patients in the saxagliptin group were treated with saxagliptin tablets 5 mg per day and one time a day. The acarbose group was treated with acarbose 50 mg，3 times a day. Follow-up observation period lasted for 24 weeks，with one follow-up in every 4 weeks. The changes of FPG，2 hPG and HbA1c before and after treatment were observed and the incidence of drug-related adverse events during the follow-up was recorded. The changes of the above indicators in the two groups were compared. Results ①The levels of FPG and 2 hPG in the saxagliptin group and acarbose group after treatment significantly decreased compared with that before the treatment （P＜0.05）. the 2 hPG level of the saxagliptin group decreased more obviously than that of the acabose group after treatment （P＜0.05）. ②After 24 weeks of intervention，the levels of HbA1c in the two groups were significantly decreased（P＜0.05），and that of the saxagliptin group decreased more than that of the acarbose group（P＜0.05），the HbA1c level of the

saxagliptin group was 48.82%，significantly higher than the acarbose group of 35.20% and the difference was statistically significant （P＜0.05）. ③During the follow-up period，the incidence of gastrointestinal abnormalities in the acarbose group was higher than that in the saxagliptin group （16.80% vs 3.94%，P＜0.05）；There was no significant difference between the two groups in incidences of hypoglycemia and other adverse events （7.09% vs 6.40%，5.51% vs 4.80%，P>0.05）. Conclusion For patients with type 2 diabetes of inadequately controlled with metformin，the application of saxagliptin can be effectively control the glucose，increase the glycosylated hemoglobin compliance rate，and will not increase the risk of hypoglycemia and gastrointestinal reactions.[Key words] Dipeptidyl peptidase inhibitor；Saxagliptin；Type 2 diabetes

糖尿病对公共健康的整体负面影响巨大。最新一项持续7年中国慢病前瞻性研究公布[1]，在我国成年人中，糖尿病患病率高，与多种心血管和非血管疾病死亡率增加具有相关性。因此，需要有效策略来降低这一疾病造成的负担。多项循证医学证据表明，严格控制血糖糖化血红蛋白（Hemoglobin A1c，HbA1c）控制在0.05），具有可比性。该研究调查方案经南安市医院伦理委员会审核通过。所有受试者自愿并签署书面知情同意书。

1.2 治疗方案

试验期间，两组患者均继续维持二甲双胍治疗，并由糖尿病专科护士进行糖尿病饮食运动的规范指导以及血糖仪的使用。在原降糖方案的基础上，沙格列汀组患者加用沙格列汀片（批准文号H20110230）5 mg/d，1次/d；阿卡波糖组加用阿卡波糖片（批准文号H1999 0205）50 mg，3次/d。随访观察期24周。每4周随访1次，用药期间密切观察药物的不良反应。

1.3 评估指标

随访期为24周。治疗前后检测所有受试者的糖化血红蛋白（HbA1c），空腹血糖（fasting plasma glucose，FBG），餐后2 h血糖（2-hours postprandial blood glucose，2 hPG）、体重指数（body mass index，BMI）等指标。记录随访期间发生低血糖事件以及胃肠道不良反应的例数。低血糖事件定义为糖尿病患者报告有低血糖某一典型症状且血糖水平0.05）。

3 讨论

英国糖尿病前瞻性研究[2]（UKPDS）结果顯示，2型糖尿病是一类进行性疾病，随着糖尿病病程的延长，患者的胰岛β细胞功能不断下降，HbA1c水平会逐步增高。随着治疗时间的延长，单药治疗无法实现血糖长期控制。联合治疗方案有助于血糖的早期达标和长期稳定。2017年美国糖尿病协会（ADA）推荐在单药二甲双胍控制HbA1c 3个月未达标者，开始两药联合治疗。糖苷酶抑制剂为传统降糖药，但其胃肠道反应较为明显。DPP-4i是一类新型口服降糖药，该研究通过沙格列汀联合二甲双胍降糖对HbA1c控制不达标的T2DM患者进行