Metformin Hydrochloride Label Adds Boxed Warning for Lactic Acidosis

The U.S. Food and Drug Administration (FDA) updated the label for canagliflozin and metformin hydrochloride extended-release (e.g., Invokamet XR) on 2026-08-11 to include a new boxed warning. This warning explicitly states: "WARNING: LACTIC ACIDOSIS Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle."

Background

The updated label applies to combination products containing canagliflozin and metformin hydrochloride, which are used for the management of type 2 diabetes. Metformin Hydrochloride is a well-established medication, and canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor. The addition of this boxed warning is a significant safety update regarding the risk of lactic acidosis specifically associated with metformin. This risk has been observed in postmarketing cases, underscoring its clinical importance. Other related drugs in the SGLT2 inhibitor class include dapagliflozin and empagliflozin.

What this means

The addition of a boxed warning to the label of canagliflozin and metformin hydrochloride combination products underscores the critical importance for healthcare providers to be vigilant for signs and symptoms of metformin-associated lactic acidosis in patients. The warning highlights that the onset of this condition can be subtle, emphasizing the need for prompt recognition and management to mitigate severe outcomes. Clinicians should be aware that postmarketing cases have reported serious consequences such as death, hypothermia, hypotension, and resistant bradyarrhythmias. This update reinforces the necessity for careful patient selection and monitoring, especially considering factors that may predispose patients to lactic acidosis when prescribing or continuing treatment with metformin-containing medications.

Source

This information is based on an FDA label revision for canagliflozin and metformin hydrochloride extended-release, effective 2026-08-11. The source document is available on dailymed.nlm.nih.gov.