Metformin-associated lactic acidosis rare but fatal if not treated early

Metformin is the most commonly prescribed oral hypoglycemic agent for the management of diabetes. It is generally considered to be a very safe drug.But rarely patients may encounter metformin induced toxicity but due to  lack of randomized control trials, most of the data pertaining to the clinical course, therapeutic interventions and outcomes of patients in such cases has come from case reports or series.

In a new meta analysis conducted by Deven Juneja and team, it has been found that individuals using metformin experienced toxicity menifested by an abrupt decline in renal function. These individuals are at risk of developing severe lactic acidosis, which can result in considerable morbidity and the need for organ transplantation. Further Metformin can cause significant toxicity, even with therapeutic doses.

The findings of this study were published in the World Journal of Diabetes.

The researchers carried out this study  to examine the symptomatology, therapeutic treatments, and outcomes of patients who presented with severe metformin toxicity by analyzing published case reports and series.

A systematic search was conducted using the terms "metformin" AND "toxicity" OR "overdose" OR "lactic acidosis" OR "hyperlactatemia" in the PubMed, Science Direct, Reference Citation Analysis, and Google Scholar databases. (1) Case reports or case series with individual patient data; and (2) Confirmed toxicity or overdose of metformin in adults, published in the English language, were the inclusion criteria. The following information was gathered: clinical presentation, baseline demographics, therapeutic treatments, intensive care unit course, and overall result.

The key findings of this study were:

1. Two hundred forty-two individual cases from 158 case reports and 26 case series were studied, with a cumulative death rate of 19.8%.

2. Diabetics on metformin comprised 214 (88.4%) of the patients.

3. Although 57 (23.6%) experienced acute ingestion, the vast majority (76.4%) were on therapeutic doses of metformin when they acquired toxicity.

4. Metformin-associated lactic acidosis (MALA) was the most often reported side event, with 224 (92.6%) individuals experiencing it.

5. The majority of the patients exhibited gastrointestinal and neurological symptoms, and a considerable proportion had acute metabolic acidosis and hyperlactatemia.

6. Renal replacement therapy (RRT) (68.6%), vasopressors (58.7%), and invasive mechanical ventilation (52.9%) were employed for organ support.

7. The vast majority of patients (68.6%) were given RRT for toxin elimination, renal dysfunction, and MALA correction.

In conclusion, despite severe MALA and the requirement for multiple organ support, they may have favorable outcomes, particularly if renal replacement therapy is administered. Metformin dosage, serum pH, lactate, and metformin levels may suggest the degree of toxicity and the necessity for strong treatment approaches, although they do not always imply unfavorable results.

Reference: 

Juneja, D., Nasa, P., & Jain, R. (2022). Metformin toxicity: A meta-summary of case reports. In World Journal of Diabetes (Vol. 13, Issue 8, pp. 654–664). Baishideng Publishing Group Inc. https://doi.org/10.4239/wjd.v13.i8.654