本文由小咖机器人翻译整理

期刊来源：BMJ

原文链接：https://doi.org/10.1136/bmj-2023-077097

摘要内容如下：

客观

在常规临床实践中，比较在二甲双胍基础上加用三种常用口服抗糖尿病药物对需要二线治疗的2型糖尿病患者的疗效。

设计

模拟比较有效性试验的队列研究（TARGET试验）。

设置

2015-21年英格兰初级保健、医院和死亡数据的关联。

参与者

75739例成人2型糖尿病患者，在二甲双胍基础上加用磺酰脲类、DPP-4抑制剂或SGLT-2抑制剂，开始二线口服抗糖尿病治疗。

主要结果指标

主要转归是基线和一年随访之间糖化血红蛋白（HbA1c）的绝对变化。次要转归是1年和2年时身体质量指数（BMI）、收缩压和估计肾小球滤过率（EGFR）的变化，2年时HbA1c的变化，EGFR下降≥40%的时间，主要不良肾脏事件，因心力衰竭住院，主要不良心血管事件（MACE）和全因死亡率。使用工具变量分析来降低由于未观察到的基线测量而产生的混杂风险。

结果

75739人开始使用磺脲类药物（n=25693，33.9%）、DPP-4抑制剂（n=34464，45.5%）或SGLT-2抑制剂（n=15582，20.6%）进行二线口服抗糖尿病治疗。SGLT-2抑制剂在降低基线和一年之间的平均HbA1c值方面比DPP-4抑制剂或磺脲类药物更有效。工具变量分析后，SGLT-2抑制剂与磺脲类药物相比，基线和一年之间HbA1c变化的平均差异为-2.5 mmol/mol（95%置信区间（CI）-3.7至-1.3），SGLT-2抑制剂与DPP-4抑制剂相比，基线和一年之间HbA1c变化的平均差异为-3.2 mmol/mol（-4.6至-1.8）。在降低BMI和收缩压方面，SGLT-2抑制剂比磺脲类或DPP-4抑制剂更有效。对于一些次要终点，缺乏SGLT-2抑制剂更有效的证据-例如，MACE的风险比为0.99（95%CI 0.61至1.62）与磺脲类药物相比，为0.91（95%CI 0.51至1.63）与DPP-4抑制剂相比。与DPP-4抑制剂（0.32，0.12至0.90）和磺脲类药物（0.46，0.20至1.05）相比，SGLT-2抑制剂降低了心力衰竭的住院风险。EGFR下降≥40%的风险比表明与磺脲类药物相比具有保护作用（0.42，0.22至0.82），与DPP-4抑制剂相比，估计的风险比具有很高的不确定性（0.64，0.29至1.43）。

结论

这项TARGET试验的仿真研究发现，SGLT-2抑制剂在降低平均糖化血红蛋白（HbA1c）、体重指数（BMI）和收缩压以及降低因心力衰竭（V DPP-4抑制剂）和肾脏疾病进展（v磺脲类药物）而住院的风险方面比磺脲类药物或DPP-4抑制剂更有效，并且没有证据表明在其他临床终点方面存在差异。

英文原文如下：

Abstracts

OBJECTIVE  To compare the effectiveness of three commonly prescribed oral antidiabetic drugs added to metformin for people with type 2 diabetes mellitus requiring second line treatment in routine clinical practice.

DESIGN  Cohort study emulating a comparative effectiveness trial (target trial).

SETTING  Linked primary care, hospital, and death data in England, 2015-21.

PARTICIPANTS  75 739 adults with type 2 diabetes mellitus who initiated second line oral antidiabetic treatment with a sulfonylurea, DPP-4 inhibitor, or SGLT-2 inhibitor added to metformin.

MAIN OUTCOME MEASURES  Primary outcome was absolute change in glycated haemoglobin A1c (HbA1c) between baseline and one year follow-up. Secondary outcomes were change in body mass index (BMI), systolic blood pressure, and estimated glomerular filtration rate (eGFR) at one year and two years, change in HbA1c at two years, and time to ≥40% decline in eGFR, major adverse kidney event, hospital admission for heart failure, major adverse cardiovascular event (MACE), and all cause mortality. Instrumental variable analysis was used to reduce the risk of confounding due to unobserved baseline measures.

RESULTS  75 739 people initiated second line oral antidiabetic treatment with sulfonylureas (n=25 693, 33.9%), DPP-4 inhibitors (n=34 464 ,45.5%), or SGLT-2 inhibitors (n=15 582, 20.6%). SGLT-2 inhibitors were more effective than DPP-4 inhibitors or sulfonylureas in reducing mean HbA1c values between baseline and one year. After the instrumental variable analysis, the mean differences in HbA1c change between baseline and one year were -2.5 mmol/mol (95% confidence interval (CI) -3.7 to -1.3) for SGLT-2 inhibitors versus sulfonylureas and -3.2 mmol/mol (-4.6 to -1.8) for SGLT-2 inhibitors versus DPP-4 inhibitors. SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in reducing BMI and systolic blood pressure. For some secondary endpoints, evidence for SGLT-2 inhibitors being more effective was lacking-the hazard ratio for MACE, for example, was 0.99 (95% CI 0.61 to 1.62) versus sulfonylureas and 0.91 (0.51 to 1.63) versus DPP-4 inhibitors. SGLT-2 inhibitors had reduced hazards of hospital admission for heart failure compared with DPP-4 inhibitors (0.32, 0.12 to 0.90) and sulfonylureas (0.46, 0.20 to 1.05). The hazard ratio for a ≥40% decline in eGFR indicated a protective effect versus sulfonylureas (0.42, 0.22 to 0.82), with high uncertainty in the estimated hazard ratio versus DPP-4 inhibitors (0.64, 0.29 to 1.43).

CONCLUSIONS  This emulation study of a target trial found that SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in lowering mean HbA1c, BMI, and systolic blood pressure and in reducing the hazards of hospital admission for heart failure (v DPP-4 inhibitors) and kidney disease progression (v sulfonylureas), with no evidence of differences in other clinical endpoints.

-----------分割线---------

点击链接：https://www.mediecogroup.com/community/user/vip/categories/ ，成为医咖会员，获取12项专属权益。