Baechle Christina, Scherler Wiebke, Lang Alexander, Filla Tim, Kuss Oliver
Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany.
German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
Acta Diabetol. 2022 Oct;59(10):1257-1263. doi: 10.1007/s00592-022-01887-y. Epub 2022 May 9.
Hemoglobin A1c (HbA1c) has been repeatedly questioned as a valid surrogate marker, especially for patient-relevant outcomes. The aim of this study was to validate the HbA1c value as a surrogate for all-cause mortality in people with type 2 diabetes.
The effect estimates for HbA1c lowering after treatment as well as reductions in all-cause mortality of randomized trials were extracted from a systematic review and updated. For the measurement of actual surrogacy, weighted linear regression models with a random intercept for the study effect were used with the all-cause mortality estimate (risk difference and log relative risk) as the outcome and the estimate for HbA1c difference as the covariate. Surrogacy was assessed according to the criteria of Daniels and Hughes.
A total of 346 HbA1c-mortality-pairs from 205 single randomized trials were included in the analysis. Regarding the risk difference of all-cause mortality, there was no evidence for surrogacy of the HbA1c value. For the log relative risk, a small positive association between HbA1c and the all-cause mortality estimate (slope 0.129 [95% confidence interval -0.043; 0.302]) was observed. However, there was no sign of valid surrogacy.
Based on the results of more than 200 randomized trials, HbA1c is not a valid surrogate marker for all-cause mortality in people with type 2 diabetes.
糖化血红蛋白（HbA1c）作为一种有效的替代标志物一直备受质疑，尤其是对于与患者相关的结局。本研究的目的是验证HbA1c值作为2型糖尿病患者全因死亡率的替代指标。
从一项系统评价中提取并更新治疗后HbA1c降低的效应估计值以及随机试验中全因死亡率的降低情况。为了衡量实际替代情况，使用具有研究效应随机截距的加权线性回归模型，将全因死亡率估计值（风险差和对数相对风险）作为结局，将HbA1c差异估计值作为协变量。根据丹尼尔斯和休斯的标准评估替代情况。
分析纳入了来自205项单项随机试验的共346对HbA1c-死亡率数据。关于全因死亡率的风险差，没有证据表明HbA1c值具有替代作用。对于对数相对风险，观察到HbA1c与全因死亡率估计值之间存在小的正相关（斜率0.129 [95%置信区间-0.043；0.302]）。然而，没有有效替代的迹象。
基于200多项随机试验的结果，HbA1c不是2型糖尿病患者全因死亡率的有效替代标志物。
