Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK.
Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK.
Lancet Diabetes Endocrinol. 2018 Oct;6(10):821-832. doi: 10.1016/S2213-8587(18)30025-1. Epub 2018 Feb 28.
Sulphonylureas have been commercially available since the 1950s, but their use continues to be associated with controversy. Although adverse cardiovascular outcomes in some observational studies have raised concerns about sulphonylureas, findings from relatively recent, robust, and high-quality systematic reviews have indicated no increased risk of all-cause mortality associated with sulphonylureas compared with other active treatments. Results from large, multicentre, randomised controlled trials such as the UK Prospective Diabetes Study and ADVANCE have confirmed the microvascular benefits of sulphonylureas, a reduction in the incidence or worsening of nephropathy and retinopathy, and no increase in all-cause mortality, although whether these benefits were due to sulphonylurea therapy and not an overall glucose-lowering effect could not be confirmed. A comparison of sulphonylureas and pioglitazone in the TOSCA.IT trial also confirmed the efficacy and cardiovascular safety of sulphonylureas. Investigators of randomised controlled trials have reported an increased risk of hypoglycaemia and weight gain with sulphonylureas, but data from observational studies suggest that the incidence of severe hypoglycaemia is lower in people taking sulphonylurea than in people taking insulin, and weight gain with sulphonylureas has been relatively modest in large cohort studies. 80% of people with diabetes live in low-to-middle income countries, so the effectiveness, affordability, and safety of sulphonylureas are particularly important considerations when prescribing glucose-lowering therapy. Results of ongoing head-to-head studies with new drugs, such as the comparison of glimepiride with linagliptin in the CAROLINA study and the comparison of various therapies (including sulphonylureas) for glycaemic control in the GRADE study, will determine the place of sulphonylureas in glucose-lowering therapy algorithms for patients with type 2 diabetes.
自 20 世纪 50 年代以来，磺酰脲类药物已在商业上应用，但它们的使用仍然存在争议。尽管一些观察性研究中出现的不良心血管结局引起了人们对磺酰脲类药物的担忧，但最近的、稳健的、高质量的系统评价结果表明，与其他活性治疗相比，磺酰脲类药物与全因死亡率增加无关。UKPDS 和 ADVANCE 等大型、多中心、随机对照试验的结果证实了磺酰脲类药物在微血管方面的益处，可降低肾病和视网膜病变的发生率或恶化程度，且全因死亡率没有增加，尽管这些益处是否归因于磺酰脲类药物治疗而不是整体降低血糖作用，尚无法确认。TOSCA.IT 试验中磺酰脲类药物与吡格列酮的比较也证实了磺酰脲类药物的疗效和心血管安全性。随机对照试验的研究者报告称，磺酰脲类药物会增加低血糖和体重增加的风险，但观察性研究的数据表明，服用磺酰脲类药物的人发生严重低血糖的风险低于服用胰岛素的人，且在大型队列研究中，磺酰脲类药物引起的体重增加相对较小。80%的糖尿病患者生活在中低收入国家，因此，在开具降血糖治疗药物时，磺酰脲类药物的有效性、可负担性和安全性尤为重要。正在进行的与新药的头对头研究的结果，如 CAROLINA 研究中格列美脲与利格列汀的比较以及 GRADE 研究中各种治疗方法（包括磺酰脲类药物）对血糖控制的比较，将确定磺酰脲类药物在 2 型糖尿病患者的降血糖治疗算法中的地位。
