High risk and low prevalence diseases: Metformin toxicities.

INTRODUCTION: Metformin toxicity is a rare but serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of metformin toxicity, including diagnosis, initial resuscitation, and management in the emergency department (ED) based on current evidence. DISCUSSION: Metformin is a common medication used for treatment of diabetes mellitus. Metformin toxicity is a spectrum of conditions that may be differentiated into three subgroups: metformin-associated lactic acidosis (MALA), metformin-induced lactic acidosis (MILA), and metformin-unrelated lactic acidosis (MULA). MILA is a condition found predominantly in patients chronically taking metformin or those with large acute overdoses. Conversely, MULA occurs in patients on metformin but with a critical illness stemming from a separate cause. MALA is rare but the most severe form, with mortality rates that reach 50%. Differentiating these entities is difficult in the ED setting without obtaining metformin levels. Patients with metformin toxicity present with nonspecific gastrointestinal symptoms and vital sign abnormalities. Laboratory analysis will reveal a high lactate with anion gap metabolic acidosis. Patients presenting with elevated lactate levels in the setting of metformin use should be considered at risk for the most severe form, MALA. Patients with MALA require aggressive treatment with intravenous fluids, treatment of any concomitant condition, and early consideration of hemodialysis, along with specialist consultation such as nephrology and toxicology. CONCLUSIONS: An understanding of metformin toxicity can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

Metformin Toxicity Leading to Severe Refractory Hyperkalemia and Metabolic Acidosis: A Case Report.

Metformin is a widely prescribed, oral, anti-diabetic agent for the treatment of type 2 diabetes mellitus (DM2). While generally well-tolerated, metformin can accumulate in patients with acute kidney injury (AKI) or chronic kidney disease (CKD), leading to potentially life-threatening complications such as metformin-associated lactic acidosis (MALA). Severe hyperkalemia is a rare but serious manifestation of metformin toxicity. We report a case of a 74-year-old African American man with DM2, hypertension, and CKD stage 3a, who presented with nausea, vomiting, lethargy, and diarrhea. Laboratory findings revealed severe AKI with a creatinine level of 8 mg/dL (baseline 1.7 mg/dL) and a potassium level of 7.8 mEq/L. The patient developed refractory hyperkalemia requiring multiple interventions and eventually continuous renal replacement therapy. Further evaluation revealed metformin-induced severe lactic acidosis with a metformin level of 21 mcg/mL (therapeutic range <5 mcg/mL). This case highlights the importance of recognizing metformin toxicity as a potential cause of severe, refractory hyperkalemia and metabolic acidosis in patients with AKI or CKD. Early recognition and prompt discontinuation of metformin, along with appropriate management of electrolyte disturbances and metabolic derangements, are crucial in preventing life-threatening complications.

Metformin-Induced Acute Hepatitis.

Metformin is considered an initial oral pharmacotherapy of choice for treating hyperglycemia in type 2 diabetes mellitus (T2DM). Although safe in the vast majority of the population, rare side effects will come to light as the prevalence of T2DM continues to rise. We present a rare case of metformin-induced hepatotoxicity and possibly the first reported case of dose-dependent metformin-induced hepatotoxicity. This case report aims to make clinicians aware of this infrequent yet significant adverse reaction that can arise with metformin therapy.