Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 106, Issue -, Pages 1227-1235Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2018.07.085
Keywords
Gluconeogenesis; Insulin sensitivity; Mechanism; Metformin; Type 2 diabetes (T2D)
Funding
- Fundamental Research Funds for the Central Universities [JUSRP11863]
- National Natural Science Foundation for Young Scientists of China [81703806]
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Type 2 diabetes (T2D) is the most common type of diabetes mellitus and is mainly characterized by insulin resistance, beta-cell dysfunction, and elevated hepatic glucose output. Metformin is a first-line antihyperglycemic agent that works mainly by regulating hepatic glucose production and peripheral insulin sensitivity. Metformin has been clinically applied for more than half a century, although the underlying pharmacological mechanisms remain elusive. This current review mainly focused on the development history of metformin and related preclinical studies on structural modification, pharmacological mechanisms for treatment of T2D, toxicology, pharmacokinetics, and pharmaceutics. The pharmacological function of metformin in lowering hyperglycemia suggests that multi-targeting could be an effective strategy for the discovery of new anti-diabetic drugs. A number of discoveries have revealed the pharmacologic mechanisms of metformin; however, precise mechanisms remain unclear. Deeper investigations on the biological features of metformin are expected to provide more rational applications and indications of this evergreen anti-T2D agent, which will in turn help to better understand the complicated pathogenesis of T2D.
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