Published online Aug 15, 2022. doi: 10.4239/wjd.v13.i8.654
Peer-review started: March 22, 2022
First decision: May 11, 2022
Revised: May 17, 2022
Accepted: July 25, 2022
Article in press: July 25, 2022
Published online: August 15, 2022
Metformin 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.
Despite severe acidosis, patients with metformin associated lactic acidosis (MALA) may have good clinical outcomes, if it is recognized early and aggressive resuscitation measures are initiated.
This study aimed to analyse the symptomology, clinical interventions and outcomes of patients presenting with severe metformin toxicity by reviewing the published case reports and series.
We performed a systematic search from PubMed, Science Direct, Reference Citation Analysis (https://www.referencecitationanalysis.com/) and Google Scholar databases using the terms “metformin” AND “toxicity” OR “overdose” OR “lactic acidosis” OR “hyperlactatemia”. The inclusion criteria were case reports or case series with individual patient details; and reported toxicity or overdose of metformin in adults, published in the English language. Data regarding baseline demographics, clinical presentation, therapeutic interventions, intensive care unit course and overall outcome were collected.
Two hundred forty-two individual cases were analyzed, 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 76.4% were on metformin in therapeutic doses when they developed toxicity. MALA was the most commonly reported adverse effect present in 224 (92.6%) patients. Patients with lowest pH and highest serum lactate and metformin levels also had favorable outcomes with use of renal replacement therapy.
Most of the reported cases were on therapeutic doses of metformin but developed toxicity after an acute deterioration in renal function. 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 renal replacement therapy 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.
Larger trials may be required to identify the risk factors associated with poor outcomes in patients with MALA.