18F-FDG uptake in the colon is modulated by metformin but not associated with core body temperature and energy expenditure

Abstract

PurposePhysiological colonic 18F-fluorodeoxyglucose (18F-FDG) uptake is a frequent finding on 18F-FDG positron emission tomography computed tomography (PET-CT). Interestingly, metformin, a glucose lowering drug associated with moderate weight loss, is also associated with an increased colonic 18F-FDG uptake. Consequently, increased colonic glucose use might partly explain the weight losing effect of metformin when this results in an increased energy expenditure and/or core body temperature. Therefore, we aimed to determine whether metformin modifies the metabolic activity of the colon by increasing glucose uptake.MethodsIn this open label, non-randomized, prospective mechanistic study, we included eight lean and eight overweight males. We measured colonic 18F-FDG uptake on PET-CT, energy expenditure and core body temperature before and after the use of metformin. The maximal colonic 18F-FDG uptake was measured in 5 separate segments (caecum, colon ascendens,—transversum,—descendens and sigmoid).ResultsThe maximal colonic 18F-FDG uptake increased significantly in all separate segments after the use of metformin. There was no significant difference in energy expenditure or core body temperature after the use of metformin. There was no correlation between maximal colonic 18F-FDG uptake and energy expenditure or core body temperature.ConclusionMetformin significantly increases colonic 18F-FDG uptake, but this increased uptake is not associated with an increase in energy expenditure or core body temperature. Although the colon might be an important site of the glucose plasma lowering actions of metformin, this mechanism of action does not explain directly any associated weight loss.

Interim [18F]FDG PET/CT can predict response to anti-PD-1 treatment in metastatic melanoma

“…It is well known that enhanced colon [ 18 F]FDG uptake of benign etiology is frequently observed in asymptomatic individuals [ 53 , 54 ]. Moreover, several studies have shown that patients using the oral hypoglycemic drug metformin tend to have a diffusely increased tracer uptake in the colon [ 55 – 58 ]. In the present cohort, no patient had diabetes; thus, metformin can be ruled out as a cause for false-positive [ 18 F]FDG accumulation in the colon.…”

Mechanisms of action of metformin with special reference to cardiovascular protection

“…It has been suggested that this anaerobic metabolism, which generates relatively little ATP, effectively amounts to a futile cycle of glucose metabolism that may contribute to weight loss commonly observed during metformin treatment . Conversely, prospective data from nondiabetic subjects showed that uptake of metformin into the gut was not associated with increased energy expenditure and thus may not contribute to the weight loss that has been observed during treatment with metformin …”

“…22,26 Conversely, prospective data from nondiabetic subjects showed that uptake of metformin into the gut was not associated with increased energy expenditure and thus may not contribute to the weight loss that has been observed during treatment with metformin. 27 Clinical studies have confirmed that the antihyperglycaemic action of immediate-release 28 or prolonged-release 29 metformin on blood glucose is dose-dependent but not related clearly to systemic exposure to metformin, as measured by plasma concentration-time curves. 30 This is especially so at higher metformin doses, consistent with a local antihyperglycaemic effect of unabsorbed metformin within the intestine.…”

The Mechanism of Action of Biguanides: New Answers to a Complex Question

“…Two different studies measured glucose uptake in diabetic patients or healthy volunteers treated with metformin using [18F]-fluoro-2-deoxy-D-glucose (FDG), a non-metabolized glucose analog. PET-computed tomography revealed a three-fold increase in FDG uptake in the small intestine and especially in the colon [122,123].…”