A boxed warning regarding lactic acidosis has been added to the label for Metformin Hydrochloride, effective July 10, 2026. This warning highlights postmarketing cases of metformin-associated lactic acidosis that have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, characterized by non-specific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain, which may be accompanied by non-specific laboratory findings.
Background
Metformin Hydrochloride is a widely used medication, often found in combination products such as Invokamet and Invokamet XR, where it is co-formulated with Canagliflozin. Other related drugs include dapagliflozin and empagliflozin. The presence of a boxed warning on a drug's label indicates a serious or potentially life-threatening adverse reaction, or other serious risk, for which the FDA believes that the risk can be prevented or reduced by appropriate use of the drug.
What this means
The addition of a boxed warning for lactic acidosis to the Metformin Hydrochloride label signifies a critical safety update for prescribers and patients. This warning emphasizes the potential for severe, life-threatening adverse events, including death, associated with metformin use. Clinicians should be vigilant for symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain, in addition to hypothermia, hypotension, and resistant bradyarrhythmias, as the onset of metformin-associated lactic acidosis can be subtle. This update underscores the importance of careful patient selection, monitoring for risk factors of lactic acidosis, and prompt recognition and management of symptoms when prescribing medications containing Metformin Hydrochloride.
Source
This information is based on an FDA label revision for Metformin Hydrochloride, effective July 10, 2026. The details of the boxed warning are available on dailymed.nlm.nih.gov.