Metformin action in the gut-insight provided by [¹⁸F]FDG PET imaging

Suppression of hepatic gluconeogenesis is thought to largely underlie the antidiabetes action of metformin. However, this drug also exerts various effects on the gut, one of which is the enhancement of the uptake of ¹⁸F-labeled fluorodeoxyglucose (FDG), a nonmetabolizable glucose derivative, during [¹⁸F]FDG positron emission tomography (PET)-computed tomography (CT). Whereas the relevance of this effect to the glucose-lowering action of metformin remains unclear, it is of special interest because it was discovered in humans. Cessation of metformin treatment for several days is required to normalize [¹⁸F]FDG uptake in the intestine, suggesting that the enhanced uptake is not a direct effect of the drug in the circulation but rather a prolonged secondary effect. A recent study with state-of-the-art PET-magnetic resonance imaging (MRI), which provides better tissue registration and soft-tissue contrast compared with PET-CT, revealed that metformin-induced accumulation of [¹⁸F]FDG occurs primarily in the lumen of the intestine, indicating that the drug promotes excretion of glucose from the circulation into this space. This phenomenon does not necessarily imply that metformin stimulates the removal of glucose from the body in the stool. Instead, it might be related to changes in the abundance and metabolism of the gut microbiota induced by metformin. Further studies of this effect of metformin might shed light on the unanswered questions that still remain concerning the clinical action of this old drug.