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

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Abstract

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.

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Authors and Affiliations

  1. Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Hitomi Tsuchida, Yasuko Morita & Wataru Ogawa

  2. Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan

    Munenobu Nogami

Authors
  1. Hitomi Tsuchida
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  2. Yasuko Morita
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  3. Munenobu Nogami
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  4. Wataru Ogawa
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Correspondence to Wataru Ogawa.

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Conflicts of interest

WO has received lecture fees from Dainippon-Sumitomo Pharma, Novartis, Nippon Boehringer Ingelheim, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, and Abbott Japan as well as research funding from Noster, Nippon Boehringer Ingelheim, Boehringer Ingelheim Pharma GmbH & Co. KG, Nippon Eli-Lilly, Novo Nordisk Pharma, Abbott Japan, Abbott Diabetes Care UK Ltd, Dainippon-Sumitomo Pharma. WO has received subsidies or donations from Kowa Pharmaceutical, Novo Nordisk Pharma, Astellas, Dainippon-Sumitomo Pharma, Ono Pharmaceutical, Takeda Pharmaceutical, Abbott Japan, Novartis, Daiichi Sankyo, Nippon Eli-Lilly, Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim. The remaining authors (HT, YM, and MN) declare that they have no conflict of interest.

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Tsuchida, H., Morita, Y., Nogami, M. et al. Metformin action in the gut―insight provided by [18F]FDG PET imaging. Diabetol Int 13, 35–40 (2022). https://doi.org/10.1007/s13340-021-00545-y

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