Objective: In addition to the inhibition of gluconeogenesis in the liver, metformin exerts various effects on the gut that likely contribute to the lowering of blood glucose levels. Positron emission tomography (PET)-computed tomography recently has revealed that metformin promotes the intestinal accumulation of [18F]fluorodeoxyglucose (FDG), a nonmetabolizable glucose derivative, indicating that the drug affects glucose handling in the intestine. It has remained unknown, however, whether this accumulation occurs in the wall or intraluminal space of the intestine. We here addressed this question with the use of [18F]FDG-based PET-magnetic resonance imaging (MRI), a recently developed imaging modality with increased accuracy of registration and high soft-tissue contrast.
Methods: Among 244 individuals with type 2 diabetes who underwent PET-MRI, we extracted 24 pairs of subjects matched for age, BMI, and HbA1c level who were (metformin group) or were not (control group) receiving treatment with metformin. We evaluated accumulation of [18F]FDG in different portions of the intestine with both a visual scale and measurement of maximum standardized uptake value (SUVmax), and such accumulation within the intestinal wall or lumen was discriminated on the basis of SUVmax.
Results: SUVmax of the jejunum, ileum, and right or left hemicolon was greater in the metformin group than in the control group. [18F]FDG accumulation in the ileum and right or left hemicolon as assessed with the visual scale was also greater in the metformin group. SUVmax for the intraluminal space of the ileum and right or left hemicolon, but not that for the intestinal wall, was greater in the metformin group than in the control group.
Conclusions: Metformin treatment was associated with increased accumulation of [18F]FDG in the intraluminal space of the intestine, suggesting that this drug promotes the transport of glucose from the circulation into stool.
K. Sakaguchi: Other Relationship; Self; AstraZeneca, Novartis AG, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Y. Morita: None. M. Nogami: None. Y. Okada: None. Y. Hirota: Other Relationship; Self; Sanofi. K. Sugawara: None. Y. Tamori: None. T. Murakami: None. W. Ogawa: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharma GmbH & Co.KG, Eli Lilly Japan K.K., Kowa Company, Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Other Relationship; Self; Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited.