Metformin associated lactic acidosis: incidence and clinical correlation with metformin serum concentration measurements

Abstract

The incidence of MALA estimated from metformin serum concentration measurements in type 2 DM patients is 5-16 times higher than reported in literature. MALA is probably caused by the frequent use of metformin in the presence of risk factors for lactic acidosis. Metformin serum concentration measurements may aid in the timely diagnosis and therapy of MALA. The outcome of MALA is determined by the severity of the underlying disease, rather than by metformin itself.

Investigation of Risk Factors Affecting Lactate Levels in Japanese Patients Treated with Metformin

“…5,[7][8][9][10] Estimated rates of lactic acidosis incidence in metformin users range from 1 to 47 cases per 100000 patient-years. 11,12) Reported predisposing factors include acute kidney injury, history of lactic acidosis, hypovolemia, seizure, liver disease, alcohol abuse, acute heart failure, myocardial infarction, and shock. [13][14][15] Although lactic acidosis during metformin use has better prognosis than other types of severe lactic acidosis, 16) the mortality rate of lactic acidosis is reported to be as high as 25-50%.…”

MALAdaptive: Do We Avoid Metformin Unnecessarily?

“…While not universally observed, 21,22 several case series have reported an inverse relationship between metformin concentration and mortality, with survivors having markedly higher metformin levels than those who did not survive. 18,19,23 Furthermore, rates of surviving MALA, especially when severe, are markedly better than surviving lactic acidosis of other origins. 21,24 Thus it is possible that metformin could be protective in lactic acidosis.…”

“…Finally, a group in the Netherlands identified 16 cases of MALA and used local population data to extrapolate this to an estimated rate of 47 per 100,000 patient-years. 19 However, they did not attempt to estimate rates of lactic acidosis among those not taking metformin for comparison. Furthermore, 9 of the 16 cases had normal levels of metformin when measured, and each of the 16 cases had a potentially confounding comorbidity.…”

Lactic Acidosis in a Patient with Type 2 Diabetes Mellitus

“…In the absence of a plasma metformin level, it is impossible to definitely assess the drug's contribution. Having said that, however, our patient, like the majority of patients who present with lactic acidosis while taking metformin, had other risk factors for lactic acidosis (25,52), the most important of which may have been his decompensated congestive heart failure. The severe lactic acidosis, therefore, was probably the result of a nefarious synergy between the metformin and his decompensated congestive heart failure.…”