Metformin Overdose

• The use of metformin has increased as the curious population seeks to slow aging, prevent age-related diseases, improve blood vessel health and insulin responsiveness. 
• When a medication invades popular culture with alternative uses, the potential for accidental misuse or overdose can lead to life-threatening complications. 
• The awareness of nurses and healthcare professionals in the treatment options for metformin overdose can be lifesaving.

Metformin Overdose

For the past two decades, Glucophage (metformin), a lynchpin for managing patients with chronic non-insulin dependent diabetes, has gained new attention as an off-label treatment for polycystic ovary syndrome, prediabetes, gestational diabetes, weight gain from antipsychotic medicines and potential malignancies. 

With over 120 million people taking metformin worldwide and more than a half-decade of use as an anti-diabetic drug, the cellular mechanisms of metformin and its exerted effects have intrigued a growing population of those seeking longevity.  

In the world of longevity, the promise of delaying heart disease, cancer, and dementia garners significant attention from the life-extension curious. The use of metformin has increased as the curious population seek to slow aging, prevent age-related diseases, improve blood vessel health and insulin responsiveness. Recent studies have explored these proposed benefits of metformin. The Targeting Aging with Metformin (TAME), a nationwide clinical trial, is exploring metformin’s ability to slow aging and reduce end-of-life morbidity.  

Metformin and its active alkaloid galegine, derived from the wild Galega officinais (French lilac), began its use as a medieval herb to treat conditions from the plague to snake bites until reaching mainstream diabetic use. When a medication invades popular culture with alternative uses, the potential for accidental misuse or overdose can led to life-threatening complications.

First approved by the FDA in 1995, lactic acidosis remains the primary concern in a metformin overdose and in therapeutic use cases in patients with underlying renal disease.  

The awareness of nurses and healthcare professionals in the treatment options for metformin overdose can be lifesaving. Metformin is available in immediate-release tablets and peaks in 2 to 4 hours and extended-release tablets that peak in 6-8 hours. With a plasma half-life of 6 hours and a whole-blood half-life of 17 hours. In patients with normal renal function, metformin excretes through the urine. 

Metformin & Human Physiology

The human body strives to support a fasting plasma glucose between 60 to 100 mg/dL (3.3 to 5.6 mmol/L). Metformin is a biguanide, a first-line glucose reducing agent suppressing hepatic glucose production and increasing peripheral glucose uptake within the treatment of non-insulin-dependent diabetes mellitus (NIDDM).

Metformin promotes euglycemia and is not a hypoglycemic agent, and when used alone, is not likely to cause hypoglycemia. Though metformin can exacerbate hypoglycemia in tandem with antidiabetic medicines.  

When misused, metformin can cause life-threatening lactic acidosis with a high rate of mortality. In contrast to common agents used to treat diabetes, hypoglycemia is not an expected outcome of an overdose and metformin does not increase insulin secretion. 

A Metformin Overdose Case Study

A 23-year-old female (56kg) arrives at the emergency room forty-five minutes after ingesting fifty-four grams of her father’s metformin in an attempted suicide. In triage, the patient has significant nausea, vomiting, diarrhea, and epigastric pain. Vital signs: temp 35.7°C, pulse of 119 beats/min, blood pressure of 149/52 mm Hg, respirations twenty-nine breaths/min and 100% saturation on room air.  

First look labs include a serum glucose level of 307 mg/d, arterial blood gas (pH 7.13, PCO2 19 mm Hg, pO2 115 mm Hg, bicarbonate 13.1 mEq/L) and a blood lactate level of 7.2 mmol/L with progressing hyperglycemia. Repeat labs highlight the patients escalating metabolic acidosis (pH 6.79) and clinical decline as her serum lactate increases to 15.9 mmol/L. As metformin accumulates in the blood, lactate generation increases, followed by hypotension, hypoxia, and impaired hepatic function. The patient’s condition continues to decline.  

In this patient, the exacerbating lactic acidosis warrants escalating treatment and the emergency room physician requests urgent hemodialysis based on EXTRIP guidelines for a patient with a lactate greater than 15 to 20 mmol/L, blood pH lower than 7.1 and failure of standard supportive care measures.  

With a low molecular weight and high-water solubility, metformin overdose is a candidate for intermittent hemodialysis with bicarbonate buffer to help with the removal of lactate as well as the metformin.  

While waiting for dialysis, the patient developed a prolonged QTc, lethargy, hypotension, hypothermia, and tachypnea. After hemodialysis, the emergency department transfers the patient to the intensive care unit. 

The Bottom Line

Metformin poisoning does not have an antidote. Patient care is symptomatic and supportive, with strategies to correct the underlying acidosis while decreasing the blood levels of metformin.  

The estimated mortality of metformin-associated lactic acidosis can be as high as 80% and is associated in those with significant comorbidities and renal insufficiency.  

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