Effect of metformin treatment on brain 18F-FDG uptake: a translational study

Metformin is one of the most widely used drugs to control diabetes type 2. However, there is no indication of pausing metformin treatment before an ¹⁸F-FDG PET scan. The aim of this study is to evaluate if metformin, in both patients and mice, can alter brain ¹⁸F-FDG uptake.

In vivo ¹⁸F-FDG PET scans were carried out in male mice. Animals were treated with saline or metformin (300 mg/kg) 10 min before ¹⁸F-FDG or chronically (3 weeks) in drinking water. Separately, patients with non-pathological ¹⁸F-FDG brain scans were distributed into two groups: metformin-treated (n = 12) and control patients (n = 27). PET images were structurally normalized to brain templates, corrected to whole-brain activity, and compared using SPM12.

In mice, acute treatment induced a significant hypermetabolism in several brain regions including hippocampus (1.07 ± 0.07 vs 0.94 ± 0.08; p = 0.0002) and thalamus (1.17 ± 0.08 vs 1.00 ± 0.08; p = 0.0002). Chronic treatment increased tracer uptake only in cortical regions. Similarly, treated patients showed hypermetabolism in the temporal lobe (1.03 ± 0.04 vs 0.97 ± 0.04; p < 0.0001) and white matter and lower uptake in frontal cortical regions (1.24 ± 0.04 vs 1.28 ± 0.06; p = 0.0165). Linear regression to HbA1c showed a negative correlation to ¹⁸F-FDG uptake in frontal and parietal cortical subregions, but no correlation to temporal lobe uptake.

Our results show that metformin treatment might modify ¹⁸F-FDG uptake in temporal lobe structures. On the other hand, lower uptake in frontal cortex might be attributable to the diabetic condition. Thus, new studies modifying the treatment regimen in diabetic patients prior to performing an ¹⁸F-FDG PET are warranted.