Aim: The use of metformin has been associated with diffusely increased colonic F-18-fluorodeoxyglucose (F-18-FDG) uptake. Interestingly, metformin use is associated with moderate weight loss. It could be hypothesized that increased colonic glucose disposal is related to this weight loss. It is unknown whether other factors influence F-18-FDG uptake in the colon. The aim of this study was to retrospectively assess independent determinants of colonic F-18-FDG uptake. Methods: We retrospectively analysed 270 F-18-FDG PET-CTs which were made for diagnostic purposes. Colonic F-18-FDG uptake was assessed using a 4-point scale using the liver as a reference (1; lower, 2; similar, 3; moderately higher than hepatic activity, 4; intense diffuse increased uptake). Determinants of F-18-FDG uptake in the colon were assessed using forward logistic regression (i.e., grade 1&2 vs 3&4). Results: The patients had a mean age of 60.2 +/- 14.8 years, a BMI of 25.8 +/- 5.2 kg/m(2) and 52% were female. Most patients had a grade 2 (44%) or grade 3 (39%) F-18-FDG uptake in the colon. Diabetes mellitus type 2 was observed in 14% of the patients. In total, 5% of the patients used insulin, 12% used metformin and 5% used sulfonylurea derivatives (SU). While there seemed to be an effect of SU on F-18-FDG uptake in the ileum [OR 3.6 (95% CI: 1.3-33.1), p = 0.03], metformin was the only drug associated with F-18-FDG uptake for both the whole colon [OR 10.0 (95% CI: 2.9-34.7), p < 0.001] and all individual segments. Conclusion: Metformin use is an independent determinant of increased colonic F-18-FDG uptake, suggesting a potential role for increasing colonic glucose disposal. (C) 2016 Elsevier Ireland Ltd. All rights reserved.