Table 2.

Summary of metformin actions in tissues other than liver and related to possible beneficial effects on glucose homeostasis and energy balance.

Target	Intracellular Actions	Effects on Metabolic Health
Skeletal muscle	Increased basal glucose uptake	Possible impact on glucose utilization and plasma glucose homeostasis
	Altered BCAA catabolism
Intestine	Increased glucose uptake	Impact on glucose homeostasis and food intake
	Increased lactate production, possibly associated with a futile enterocyte-hepatocyte futile cycle (lactate-glucose)	Some side-effects associated with metformin treatment in humans
	Reduced bile acid absorption, with consequences on GLP-1 and peptide YY secretion
Gut microbiota	Changes in the relative abundance of bacterial strains, possibly associated with an impact on SCFA production	Impact on glucose homeostasis, appetite and body weight gain
Intestine and kidney	Increased expression and release of GDF15 (increased circulating levels)	Impact on energy balance and body weight gain
Medio-basal hypothalamus	Decreased AMPK activity	Impact on food intake