A Boxed Warning regarding the risk of lactic acidosis has been added to the label for Metformin ER 500 mg, effective 2026-07-17. This significant label revision highlights the potential for serious, life-threatening adverse events associated with metformin use, including death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle.

Background

Metformin is a widely used oral antihyperglycemic agent for the management of type 2 diabetes. It belongs to the biguanide class of drugs and primarily works by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. The extended-release (ER) formulation, such as Metformin ER 500 mg, allows for once-daily dosing. Lactic acidosis is a known, though rare, complication associated with metformin use, particularly in patients with predisposing conditions.

What this means

The addition of a Boxed Warning to the Metformin ER 500 mg label underscores the critical importance of recognizing and managing the risk of lactic acidosis. This severe metabolic complication, though rare, can be fatal and requires immediate medical attention. Postmarketing cases have resulted in serious outcomes including death, hypothermia, hypotension, and resistant bradyarrhythmias. Clinicians should be vigilant for symptoms such as malaise, myalgia, respiratory distress, somnolence, and abdominal distress, which may precede the onset of lactic acidosis. Patient education regarding these risks and the need to seek prompt medical care if symptoms arise is crucial. The warning also implies careful patient selection and monitoring, particularly in those with predisposing factors such as renal impairment, concomitant use of certain drugs, or conditions that may lead to hypoperfusion and hypoxemia.

Source

This information is based on an FDA label revision for Metformin ER 500 mg, effective 2026-07-17. The details are available on dailymed.nlm.nih.gov.