OBJECTIVE In clinical trials, treatment with fenofibrate did not reduce the incidence of major cardiovascular events (MCVE) in patients with type 2 diabetes mellitus (T2DM). However, treatment effects reported by trials comprise patients who respond poorly and patients who respond well to fenofibrate. Our aim was to use statistical modeling to estimate the expected treatment effect of fenofibrate for individual patients with T2DM.

RESEARCH DESIGN AND METHODS To estimate individual risk, the FIELD risk model, with 5-year MCVE as primary outcome, was externally validated in T2DM patients from ACCORD and the SMART observational cohort. Fenofibrate treatment effect was estimated in 17,142 T2DM patients from FIELD, ACCORD, and SMART. Individual treatment effect, expressed as absolute risk reduction (ARR), is the difference between treated and untreated MCVE risk. Results were stratified for patients with and without dyslipidemia (i.e., high triglycerides and low LDL cholesterol).

RESULTS External validation of the FIELD risk model showed good calibration and moderate discrimination in ACCORD (C-statistic 0.67 [95% CI 0.65–0.69]) and SMART (C-statistic 0.66 [95% CI 0.63–0.69]). Median 5-year MCVE risk in all three studies combined was 6.7% (interquartile range [IQR] 4.0–11.7) in patients without (N = 13,224) and 9.4% (IQR 5.4–16.1%) in patients with (N = 3,918) dyslipidemia. The median ARR was 2.15% (IQR 1.23–3.68) in patients with dyslipidemia, corresponding with a number needed to treat (NNT) of 47, and 0.22% (IQR 0.13–0.38) in patients without dyslipidemia (NNT 455).

CONCLUSIONS In individual patients with T2DM, there is a wide range of absolute treatment effect of fenofibrate, and overall the fenofibrate treatment effect was larger in patients with dyslipidemia. The method of individualized treatment effect prediction of fenofibrate on MCVE risk reduction in T2DM can be used to guide clinical decision making.

目的在临床试验中，非诺贝特治疗不能降低2型糖尿病（T2DM）患者主要心血管事件（MCVE）的发生率。但是，试验报告的治疗效果包括对非诺贝特反应不良的患者和对非诺贝特反应良好的患者。我们的目标是使用统计模型来估计非诺贝特对个别2型糖尿病患者的预期治疗效果。

研究设计和方法为了评估个体风险，以ACCORD和SMART观察队列的T2DM患者外部验证了以5年MCVE为主要结果的FIELD风险模型。在FIELD，ACCORD和SMART的17,142例T2DM患者中估计了非诺贝特的治疗效果。个体治疗效果表示为绝对风险降低（ARR），是已治疗和未治疗MCVE风险之间的差异。对有和没有血脂异常（即高甘油三酸酯和低LDL胆固醇）的患者进行分层。

结果FIELD风险模型的外部验证显示ACCORD（C统计0.67 [95％CI 0.65-0.69]）和SMART（C统计0.66 [95％CI 0.63-0.69]）具有良好的校准和中等判别能力。在所有三个研究合并正中5年MCVE风险为6.7％的患者（四分位数间距[IQR] 4.0-11.7）无（Ñ = 13224），并在患者的9.4％（IQR 5.4-16.1％）（ñ = 3918）血脂异常。血脂异常患者的平均ARR为2.15％（IQR 1.23–3.68），对应于需要治疗的人数（NNT）为47，而血脂异常患者的平均ARR为0.22％（IQR 0.13-0.38）（NNT 455）。

结论在个别的T2DM患者中，非诺贝特的绝对治疗效果范围很广，总的来说，在血脂异常患者中非诺贝特的治疗效果更大。预测非诺贝特对T2DM患者MCVE风险降低的个体化治疗效果的方法可用于指导临床决策。