Understanding the action mechanisms of metformin in the gastrointestinal tract

Meihui Cheng; Lili Ren; Xianxian Jia; Jianwei Wang; Bin Cong

doi:10.3389/fphar.2024.1347047

Understanding the action mechanisms of metformin in the gastrointestinal tract

Front Pharmacol. 2024 Mar 28:15:1347047. doi: 10.3389/fphar.2024.1347047. eCollection 2024.

Authors

Meihui Cheng^{1

2

3}, Lili Ren^{1

3}, Xianxian Jia^{1

4}, Jianwei Wang^{1

3}, Bin Cong^{1

2}

Affiliations

¹ Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² College of Forensic Medicine, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Medical University, Shijiazhuang, China.
³ NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁴ Department of Pathogen Biology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China.

Abstract

Metformin is the initial medication recommended for the treatment of type 2 diabetes mellitus (T2DM). In addition to diabetes treatment, the function of metformin also can be anti-aging, antiviral, and anti-inflammatory. Nevertheless, further exploration is required to fully understand its mode of operation. Historically, the liver has been acknowledged as the main location where metformin reduces glucose levels, however, there is increasing evidence suggesting that the gastrointestinal tract also plays a significant role in its action. In the gastrointestinal tract, metformin effects glucose uptake and absorption, increases glucagon-like peptide-1 (GLP-1) secretion, alters the composition and structure of the gut microbiota, and modulates the immune response. However, the side effects of it cannot be ignored such as gastrointestinal distress in patients. This review outlines the impact of metformin on the digestive system and explores potential explanations for variations in metformin effectiveness and adverse effects like gastrointestinal discomfort.

Keywords: drug mechanism; gastrointestinal tract; gut microbiota; metformin; type 2 diabetes.

Publication types

Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by the CAMS Innovation Fund for Medical Sciences (No. 2019-I2M-5-055) and the National Natural Science Foundation of China (No. 82304360).