Lactate levels with chronic metformin use: a narrative review

Metformin has been associated with lactic acidosis. Lactate levels are not commonly tested in clinical practice, and it is unclear to what extent metformin would typically increase lactate levels with chronic use. The aim of this review was to determine whether regular monitoring of the plasma lactate level would be beneficial in avoiding lactate accumulation and, ultimately, minimising the incidence of lactic acidosis in metformin-treated patients.

A comprehensive search of PubMed, Embase, Web of Science, Cochrane and International Pharmaceutical Abstracts databases covering the period up to 30 May 2017 was performed. Search terms included combinations of terms and keywords, including "metformin", "lactate", "lactic acid" and "lactic acidosis". Cases series of lactic acidosis or metformin-associated lactic acidosis were excluded.

Of 1539 potentially relevant articles, a total of 52 reported lactate levels from routine/regular pathological tests in metformin users. The studies were subdivided into four themes, regarding metformin usage and the reported lactate levels in patients who: (1) did not have contraindications to the use of metformin; (2) had contraindications, or renal impairment but without other contraindications; (3) exercised; or (4) also received any nucleoside reverse transcriptase inhibitor. Studies have reported that metformin treatment could increase lactate level of users. However, most results showed that the lactate level remained in the normal range.

No definitive conclusions on the benefits of regular lactate monitoring in patients taking metformin can be made. Future research on larger populations focusing on the measurement of lactate levels with continuous metformin use is warranted.