title: Lipid profiling reveals different therapeutic effects of metformin and glipizide in patients with type 2 diabetes and coronary artery disease.
abstract: OBJECTIVE
  We recently demonstrated a beneficial effect of metformin compared with glipizide in type 2 diabetic patients regarding cardiovascular outcomes for 3-year treatment in the SPREAD-DIMCAD study. However, the potential mechanism for the clinical effects remains unclear. Here, we performed a comprehensive lipidomics study to evaluate the different lipid metabolites in serum samples obtained from participants in this study.
  
  
  METHODS
  Liquid chromatography-quadrupole time of flight-mass spectrometry was used to evaluate the different lipid metabolites in serum samples obtained from the participants (21 patients in glipizide group and 23 patients in metformin group) before and after each year of treatment (at 0 [baseline], 1, 2, and 3 years of study drug administration).
  
  
  RESULTS
  A total of 118 serum lipid molecular species was identified and quantified. During treatment, metformin induced a substantially greater change in serum lipid species compared with glipizide, especially at the 2- and 3-year time points (with 2, 11, and 12 lipid species being significantly different between the groups after each year of treatment [1, 2, or 3 years], P < 0.05). Among the significantly changed lipid species, three lipid metabolites were linked to long-term composite cardiovascular events (adjusted P < 0.05). After treatment, triacylglycerols (TAGs) of a relatively higher carbon number showed a clearly increased trend in metformin group compared with the glipizide group, whereas the changes in TAGs with different double bonds were minimal.
  
  
  CONCLUSIONS
  Our findings revealed the differential therapeutic effects of metformin and glipizide on comprehensive lipidomics, which were comparable with their different long-term effects on cardiovascular outcomes.
authors.affiliation: Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
authors.forename: Chunxiu
authors.initials: C
authors.lastname: Hu
authors.affiliation: Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Shenghan
authors.initials: S
authors.lastname: Lai
authors.affiliation: Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
authors.forename: Ankang
authors.initials: A
authors.lastname: Lv
authors.affiliation: Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Su
authors.affiliation: Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Second Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Second Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Tang
authors.affiliation: Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Lianqun
authors.initials: L
authors.lastname: Cui
authors.affiliation: Chang Hai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Dajin
authors.initials: D
authors.lastname: Zou
authors.affiliation: First Affiliated Hospital of Wenzhou Medical College, Zhejiang Province, China.
authors.forename: Dawang
authors.initials: D
authors.lastname: Wang
authors.affiliation: Sir Run Run Shaw Hospital, Zhejiang Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Jiangsu Province Hospital, Jiangsu Province, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Guoting
authors.initials: G
authors.lastname: Wu
authors.affiliation: Nanfang Hospital, Guangdong Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Nanjin Drum Tower Hospital, Jiangsu Province, China.
authors.forename: Dalong
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Shen
authors.affiliation: Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China guangning@medmail.com.cn xugw@dicp.ac.cn.
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China guangning@medmail.com.cn xugw@dicp.ac.cn.
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D005913:Glipizide / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D008055:Lipids; D008687:Metformin; D005913:Glipizide