A boxed warning for lactic acidosis was added to the label for metformin hydrochloride, effective 2025-08-06. This significant label revision highlights postmarketing cases of metformin-associated lactic acidosis, which have been linked to severe outcomes including death, hypothermia, hypotension, and resistant bradyarrhythmias. The warning emphasizes that the onset of this condition can be subtle.
Background
Metformin hydrochloride is a medication that is also found in combination products such as Invokamet XR, Invokana, and Invokamet, which include canagliflozin. Other related drugs include dapagliflozin and empagliflozin.
What this means
The addition of a boxed warning to the metformin hydrochloride label underscores the serious risk of lactic acidosis associated with its use. This warning is based on observed postmarketing cases where metformin-associated lactic acidosis has led to severe health consequences. Specifically, these cases have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The label revision explicitly notes that the onset of metformin-associated lactic acidosis is often subtle. This subtlety means that the condition may not present with obvious or immediate symptoms, potentially delaying diagnosis and intervention. Healthcare providers should be aware of these severe potential consequences and the insidious nature of the condition's onset when prescribing or monitoring patients on metformin hydrochloride.
Source
The information regarding this label revision was obtained from the FDA, as documented on 2025-08-06. The source document is available on dailymed.nlm.nih.gov.