Recurrent hypoglycemia secondary to metformin toxicity in the absence of co-ingestions: a case report

Abstract

BackgroundMetformin toxicity is well known to cause lactic acidosis. Multiple cases of hypoglycemia due to isolated metformin overdose have been reported. Increased glucose consumption secondary to anaerobic metabolism has been reported as a possible explanation.Case presentationA 23-year-old Arabic woman took 30 g of metformin. In the emergency department, 4 hours after of the event, she was fatigued but vitally stable. During her hospitalization, she had severe lactic acidosis, hypotension corrected with fluid boluses and vasopressors, and multiple episodes of hypoglycemia (6.3 mg/dL, 38 mg/dL, and 42 mg/dL), requiring multiple 50% dextrose-water boluses. The three hypoglycemic episodes occurred coincident with severe lactic acidosis. She improved after 24 hours of continuous renal replacement therapy.ConclusionsHypoglycemia can be induced by metformin toxicity in the absence of co-ingestants. A possible explanation of metformin-induced hypoglycemia is increased glucose consumption due to anaerobic metabolism, decreased oral intake, decreased liver glucose production, and decreased glucose absorption.

Symptomatic Hypoglycemia During Treatment with a Therapeutic Dose of Metformin

“…There are case reports estimating no more than 2% rate of hypoglycemia secondary to metformin overdose or toxicity [ 4 , 5 ], but hypoglycemia at a therapeutic metformin dose is thought to be rare. Several hypotheses have been proposed for metformin-induced hypoglycemia, but are currently controversial.…”

“…Metformin-associated lactic acidosis (MALA) is a rare adverse effect reported in postmarking cases, the majority of which were linked to metformin toxicity and/or predisposing conditions such as hypovolemia, infection or sepsis, acute or chronic kidney disease, or liver cirrhosis [ 1 , 4 ]. There are reports of metformin overdose or toxicity triggering hypoglycemia, but in only 2% of the cases [ 5 ]. There are no case reports of hypoglycemia while on conventional or therapeutic doses of metformin.…”

Reactive Hypoglycemia From Metformin Immediate-Release Monotherapy Resolved by a Switch to Metformin Extended-Release: Conceptualizing Their Concentration-Time Curves

“…Metformin is the preferred initial medication for most patients with T2DM due to its overall efficacy and lack of hypoglycemia when used in monotherapy. Overall, the available case reports also suggest that clinically significant hypoglycemia is uncommon in metformin monotherapy and unlikely to occur abruptly in the absence of any predisposing conditions [ 6 - 11 ]. Indeed, there is no previous report of this phenomenon occurring merely due to Met IR, as is evident in this patient by the normal renal and liver function tests, and the absence of risk factors for hypoglycemia that include prolonged fasting, exercise, acute illness, or addition of another antidiabetic [ 1 ].…”

“…Adverse events associated with metformin use are often gastrointestinal in nature, e.g., nausea, vomiting, and occasionally diarrhea [1]. However, hypoglycemia due to overdose, decreased drug clearance, nutritional deficits, multiple comorbidities, and drug-drug interactions, is rarely known to occur [6][7][8][9][10][11]. In this report, the case of a 55-year-old diabetic patient with no known comorbidity who developed metforminassociated hypoglycemia that promptly resolved after stopping Met IR and initiating Met XR is presented.…”

Schwere Metformin-assoziierte Laktatazidose bei einem 67-jährigen Patienten

“…Es wird angenommen, dass hierbei ein gesteigerter Glukoseverbrauch im Rahmen des ausgeprägten anaeroben Metabolismus zur Hypoglykämie führt. Jedoch werden auch andere Mechanismen wie eine reduzierte Glukoseproduktion der Leber sowie eine verminderte intestinale Glukoseaufnahme diskutiert [9].…”