二甲双胍之后的选择--二线降糖药物应如何选择?聚焦磺脲类药物:联合应用与复方制剂

What's next after Metformin? Focus on Sulphonylurea: Add-on or Combination Ttherapy

目的:本综述旨在评估2型糖尿病的二线治疗药物,尤其是磺脲类药物的临床应用问题,对磺脲类药物和二甲双胍联合用药与复方制剂进行比较。方法:从数据库中检索大量的英文论著、临床实践指南以及相关参考文献。结果:磺脲类药物与二甲双胍联用可以同时改善胰岛素抵抗和胰岛素分泌不足。与噻唑烷二酮类药物、二肽基肽酶-4(dipeptidyl peptidase-4,DPP-4)抑制剂、胰高血糖素样肽-1(glucagonlike peptide 1,GLP-1)受体激动剂和胰岛素相比,磺脲类药物更加有效且价格低廉。磺脲类药物主要的不良反应为低血糖,与二甲双胍联用体重增加不明显。低剂量的磺脲类/二甲双胍的复方制剂可以更好地控制血糖,减少不良反应,具有更高的患者依从性,并且复方制剂比联合用药价格更低廉。结论:磺脲类药物作为二线药物与二甲双胍联合治疗可以针对2型糖尿病的两个主要发病环节,即胰岛素抵抗和胰岛素分泌不足,临床使用有效、安全、经济。与联合用药相比,固定剂量的复方制剂可提高患者的依从性,无论是原研药物还是仿制药物的复方制剂,均价格低廉、疗效更佳。

Objective:The aim of this review was to evaluate the drug class after metformin especially sulphonylurea and issues around add-on or fixed dose combination therapy.Methods:Extensive literature search for English language articles,clinical practice guidelines and references was performed using electronic databases.Results:Adding sulphonylurea to metformin targeted both insulin resistance and insulin deficiency.Sulphonylurea was efficacious and cheaper than thiazolidinedione,dipeptidyl peptidase-4inhibitor,glucagon-like peptide1analogue and insulin.The main side effect of sulphonylurea was hypoglycaemia but there was no effect on the body weight when combining with metformin.Fixed dose sulphonylurea/metformin was more efficacious at lower dose and reported to have fewer side effects with better adherence.Furthermore,fixed dose combination was cheaper than add-on therapy.Conclusion:sulphonylurea was feasible as the second line agent after metformin as the combination targeted on two pathways,efficacious,cost-effective and had long safety history.Fixed dose combination tablet could improve patient's adherence and offered an inexpensive and more efficacious option regardless of original or generic product as compared to add-on therapy.