What mechanisms are responsible for the effectiveness of metformin in the treatment of type 2 diabetes mellitus (DM)?

Updated: Sep 27, 2021
  • Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
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Metformin lowers basal and postprandial plasma glucose levels. Its mechanisms of action differ from those of other classes of oral antidiabetic agents; metformin works by decreasing hepatic gluconeogenesis production. It also decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

A study by Sun et al suggested that metformin also exercises glucose control by reducing levels of Bacteroides fragilis in the gut. The research indicated that reduction of the microbe, which has bile salt hydrolase activity, leads to an increase in the bile acid glycoursodeoxycholic acid (GUDCA), which in turn inhibits signaling of the intestinal farnesoid X receptor (FXR), a nuclear receptor that plays a role in regulating hepatic bile acid. [175, 176]  Unlike oral sulfonylureas, metformin rarely causes hypoglycemia.

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