Metformin significantly improves glycemia, fasting serum hyperinsulinemia and oral glucose tolerance. Starting from week 1 of treatment, food intake was reduced in all groups but predominantly in the groups receiving HFD, where the metformin group displayed the largest decrease (A). Due to the relatively short treatment period, and food intake being determined at only two time points (at the end of week 1 and week 2), statistical significance could not be calculated. The weight of the animals reflects the reduced food intake (B, C), where the weight loss is greatest in animals receiving metformin in combination with HFD. HbA1c(D) and fasting serum insulin (E) levels are significantly increased in the HFD group, and significantly reduced (20% and 60% decrease, respectively) by a 14 day oral administration of 300 mg/day metformin. Glucose tolerance (F,G) is significantly decreased in mice receiving a HFD (37% increase in plasma glucose 15 min following oral glucose load), and significantly improved following a 14 day oral administration of 300 mg/day metformin; 6% reduction in plasma glucose (n = 8 for control diet group, n = 6 for HFD group, n = 4 for HFD group receiving metformin). Bars represent mean ± SEM. * and ** denote p < 0.05 and p < 0.01, respectively, compared with control group. #, p < 0.05 compared with HFD group. Statistical analysis was performed using one-way ANOVA.