Severe hypoglycemia and hypothermia in massive metformin overdose

Metformin is a biguanide medication thought to contribute to increased insulin sensitivity. It does not induce insulin release or act via insulin receptors, so it is not considered a common cause of hypoglycemia, even in overdose. However, massive metformin overdoses may be associated with severe hypoglycemia as well as hypothermia.

Four patients who had hypoglycemia after metformin overdoses are presented. None had access to other diabetic medications or a known diagnosis of diabetes mellitus.

Severe hypoglycemia (blood glucose concentration <2.2 mmol/L [<39.6 mg/dL]) in all patients was diagnosed on presentation or within 9 h of initial presentation. Peak serum lactate concentrations were observed after hypoglycemia in each patient. Three patients developed hypothermia. Three patients received extracorporeal therapy; hemodialysis (one), continuous kidney replacement therapy (one), both modalities (one). One patient died. The remainder were discharged home within 2-6 days of presentation.

The complex mechanisms of metformin may explain the observed progression of manifestations following large metformin overdoses.

Large metformin ingestions exceeding 60 g can be associated with critically low serum glucose concentrations concurrently with or preceding increases in serum lactate concentrations. Hypothermia may also occur. Further study is needed to determine the exact mechanisms and true incidence of this manifestation, which may be underrecognized.