Huang Qi, Zou Xiantong, Chen Yingli, Gao Leili, Cai Xiaoling, Zhou Lingli, Gao Fei, Zhou Jian, Jia Weiping, Ji Linong
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.
Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai 200233, China.
iScience. 2023 Oct 12;26(11):108195. doi: 10.1016/j.isci.2023.108195. eCollection 2023 Nov 17.
Chiglitazar (carfloglitazar) is a peroxisome proliferator-activated receptor pan-agonist presenting non-inferior glucose-lowering efficacy with sitagliptin in patients with type 2 diabetes. To delineate the subgroup of patients with greater benefit from chiglitazar, we conducted a machine learning-based post-hoc analysis in two randomized controlled trials. We established a character phenomap based on 13 variables and estimated HbA decline to the effects of chiglitazar in reference to sitagliptin. Out of 1,069 patients, 63.3% were found to have greater reduction in HbA levels with chiglitazar, while 36.7% showed greater reduction with sitagliptin. This distinction in treatment response was statistically significant between groups (p<0.001). To identify patients who would gain the most glycemic control benefit from chiglitazar, we developed a machine learning model, ML-PANPPAR, which demonstrated robust performance using sex, BMI, HbA, HDL, and fasting insulin. The phenomapping-derived tool successfully identified chiglitazar responders and enabled personalized drug allocation in patients with drug-naïve diabetes.
西格列他钠（卡格列他扎）是一种过氧化物酶体增殖物激活受体全激动剂，在2型糖尿病患者中，其降血糖疗效不劣于西格列汀。为了确定能从西格列他钠中获益更多的患者亚组，我们在两项随机对照试验中进行了基于机器学习的事后分析。我们基于13个变量建立了一个特征表型图谱，并参照西格列汀评估了西格列他钠对糖化血红蛋白（HbA）下降的影响。在1069名患者中，发现63.3%的患者使用西格列他钠后HbA水平下降幅度更大，而36.7%的患者使用西格列汀后下降幅度更大。两组间这种治疗反应的差异具有统计学意义（p<0.001）。为了识别能从西格列他钠中获得最大血糖控制益处的患者，我们开发了一种机器学习模型ML-PANPPAR，该模型利用性别、体重指数、HbA、高密度脂蛋白和空腹胰岛素表现出强大的性能。基于表型图谱衍生的工具成功识别了西格列他钠反应者，并能够在初治糖尿病患者中进行个性化药物分配。
