Investigation of risk factors affecting lactate levels in Japanese patients treated with metformin

Abstract

Metformin is a biguanaide antidiabetic drug used worldwide, and its effectiveness and benefits have already been established. However, the safety of high doses of metformin in Japanese patients, especially in elderly patients with a decreased renal function, remains unclear. Among the side effects of metformin, lactate acidosis is the most problematic due to a high mortality rate. Therefore, we assessed plasma lactate levels in metformin-treated patients to identify independent risk factors for hyperlactemia. 290 outpatients receiving various doses of metformin at our hospital were enrolled between March and July 2014. Serum electrolytes, Cre (creatinine), BUN (blood urea nitrogen), UA (uric acid), HbA1c (hemoglobin A1c), and lactate levels were investigated. Lactate levels did not significantly differ between the elderly (≥75 years) and non-elderly (<75 years) groups. Patients in the elderly group had a significantly lower daily metformin dose and estimated glomerular filtration rate (eGFR), compared with the non-elderly group (both p<0.005). Between with and without hyperlactemia groups, no significant differences were observed in either Cre or age. On the other hand, patients with hyperlactemia had a significantly higher dose of metformin than those without hyperlactemia (p<0.05). In this study, we found that old age and mildly impaired kidney function were not associated with increased lactate levels, and that a higher dose of metformin may be an independent risk factor for elevated lactate levels in Japanese patients.