Figure 1.

Long-term toxicity of metformin in Mate1^+/+, Mate1^+/− and Mate1^−/− mice. Mate1^+/+ (n= 9), Mate1^+/− (n= 9) and Mate1^−/− (n= 11) mice were given 3 mg·mL⁻¹ metformin in drinking water for 21 days. The mean daily dose of each 7 days (A), body weight change from baseline (B), blood lactate level (C), pH (D) and HCO₃^- levels (E) were determined at 0, 7, 14 and 21 days after metformin treatment. Blood samples were collected under anaesthesia in 4 h-fasted mice. Blood lactate, pH and HCO₃^- levels were measured by i-STAT. Each point represents the mean ± SEM. *P < 0.05, significantly different from Mate1^+/+ mice at each day.