Dose-related effects of metformin on acid–base balance and renal function in patients with diabetes who develop acute renal failure : a cross-sectional study

Aims: The role of metformin in the development of lactic acidosis (LA) in the setting of acute renal failure (ARF) is debated. Moreover, recent experiments suggested that metformin can also be nephrotoxic, but little clinical data exist about this topic. We sought to investigate these possible associations in a large cohort of patients with diabetes who developed ARF. Methods: We analyzed data from patients with diabetes admitted to our emergency department between 2007 and 2011 with ARF and a previously normal renal function (n = 126). We compared acid\u2013base balance and renal function of patients taking metformin (n = 74) with patients not taking it (n = 52). Results: Patients taking metformin had decreased pH (7.31 \ub1 0.16 vs 7.39 \ub1 0.11, p = 0.008) and higher lactates (4.54 \ub1 4.30 vs 1.71 \ub1 1.14 mmol/L, p < 0.001). Both acidosis (pH < 7.35) and LA (lactates >5 mmol/L and pH < 7.35) were more frequently observed in this group (p = 0.0491 and p < 0.001, respectively). Multivariate analysis ruled out the role of some possible confounders, especially decreased renal function. The influence of metformin on pH and lactates grew significantly with higher doses of the drug (p = 0.259 and p = 0.092 for <1 g/day, p = 0.289 and p < 0.001 for 1\u20132 g/day, p = 0.009 and p < 0.001 for 2\u20133 g/day, for pH and lactates, respectively). Metformin influenced creatinine levels in a dose-related manner as well (p = 0.925 for <1 g/day, p = 0.033 for 1\u20132 g/day, p < 0.001 for 2\u20133 g/day). Conclusions: In patients with diabetes who were admitted to our emergency department with ARF, the use of metformin was associated in a dose-related fashion with both LA and worse renal function