Metformin toxicity: A meta-summary of case reports.

backgroundMetformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes. Due to the lack of randomized control trials, most of the data pertaining to the clinical course, therapeutic interventions and outcomes of patients with metformin induced toxicity has come from case reports or series.

aimTo analyse the symptomology, clinical interventions and outcomes of patients presenting with severe metformin toxicity by reviewing the published case reports and series.

methodsWe performed a systematic search from PubMed, Science Direct,

resultsTwo hundred forty-two individual cases were analysed, from 158 case reports and 26 case series, with a cumulative mortality of 19.8%. 214 (88.4%) patients were diabetics on metformin. 57 (23.6%) had acute ingestion, but a great majority (76.4%) were on metformin in therapeutic doses when they developed toxicity. Metformin associated lactic acidosis (MALA) was the most commonly reported adverse effect present in 224 (92.6%) patients. Most of the patients presented with gastrointestinal and neurological symptoms and a significant number of patients had severe metabolic acidosis and hyperlactatemia. The organ support used was renal replacement therapy (RRT) (68.6%), vaso-pressors (58.7%) and invasive mechanical ventilation (52.9%). A majority of patients (68.6%) received RRT for toxin removal, renal dysfunction and correction of MALA. Patients with lowest pH and highest serum lactate and metformin levels also had favourable outcomes with use of RRT.

conclusionMost of the reported cases were on therapeutic doses of metformin but developed toxicity after an acute deterioration in renal functions. These patients may develop severe lactic acidosis, leading to significant morbidity and need for organ support. Despite severe MALA and the need for multiple organ support, they may have good outcomes, especially when RRT is used. The dose of metformin, serum pH, lactate and metformin levels may indicate the severity of toxicity and the need for aggressive therapeutic measures but may not necessarily indicate poor outcomes.