Metformin toxicity: A meta-summary of case reports

BACKGROUND 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.AIM To analyse the symptomology,clinical interventions and outcomes of patients presenting with severe metformin toxicity by reviewing the published case reports and series.METHODS 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:(1)Case reports or case series with individual patient details;and(2)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.RESULTS Two 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%),vasopressors(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.CONCLUSION Most 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.

High performance of a unique mesoporous polystyrene-based adsorbent for blood purification

A multi-functional polystyrene based adsorbent(NKU-9)with a unique mesoporous and a high surface area was prepared by suspension polymerization for removal of therapeutic toxins in blood purification.The adsorbent produced had an almost equal amount of mesopore distribution in the range from 2 to 50 nm.The adsorption of serum toxins with different molecular weights were examined by in vitro adsorption assays and compared with some clinical currently used adsorbents such as HA-330,Cytosorb and BL-300 which are produced by China,America and Japan,respectively.Test results indicated that the adsorption rate for pentobarbital by NKU-9 was 81.24%which is nearly as high as HA-330(81.44%).The latter adsorbent is currently used for acute detoxification treatment in China.To reach adsorption equilibrium,NKU-9 was faster than HA-330,which implies short treatment time.For the removal of middle molecular toxins such as b2-microglobulin(98.88%),NKU-9 performed better adsorptive selectivity than Cytosorb(92.80%).In addition,NKU-9 showed high performance for the removal of albumin-bound toxins(e.g.,bilirubin),and its adsorption rate for total bilirubin(80.79%)in plasma was 8.4%higher than that of anion exchange resin BL-300 which is currently used to eliminate bilirubin in clinic.Therefore,our results indicate that the newly developed adsorbent with a wide distribution and almost equal amount of mesopores is a multifunctional adsorbent for high efficient removal of serum toxins with different molecular weights which might be an excellent blood purification adsorbent especially to treat diseases that conventional medical methods are low or not efficient.