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.

RESEARCH DESIGN AND 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: Yifei Zhang, Chunxiu Hu, Jie Hong, Jun Zeng, Shenghan Lai, Ankang Lv, Qing Su, Yan Dong, Zhiguang Zhou, Weili Tang, Jiajun Zhao, Lianqun Cui, Dajin Zou, Dawang Wang, Hong Li, Chao Liu, Guoting Wu, Jie Shen, Dalong Zhu, Weiqing Wang, Weifeng Shen, Guang Ning, Guowang Xu
• Journal: Diabetes care (Diabetes Care) Vol. 37 Issue 10 Pg. 2804-12 (Oct 2014) ISSN: 1935-5548 [Electronic] United States
• PMID: 25011952 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• Blood Glucose
• Lipids
• Metformin
• Glipizide

Topics

• Aged
• Blood Glucose (metabolism)
• Coronary Artery Disease (blood, drug therapy)
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Diabetic Angiopathies (blood, drug therapy)
• Double-Blind Method
• Female
• Glipizide (pharmacology, therapeutic use)
• Humans
• Lipids (blood)
• Male
• Metabolome (drug effects)
• Metabolomics
• Metformin (pharmacology, therapeutic use)
• Middle Aged