A boxed warning concerning metformin-associated lactic acidosis was added to the label for Invokamet XR (canagliflozin and metformin hydrochloride extended-release) on 2026-07-09. This significant label revision highlights the potential for serious, sometimes fatal, adverse events associated with metformin use, including death, hypothermia, hypotension, and resistant bradyarrhythmias.
Background
Invokamet XR is a combination medication containing canagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, and metformin hydrochloride, a biguanide. Both components are used in the management of type 2 diabetes mellitus. While canagliflozin works by reducing glucose reabsorption in the kidneys, metformin primarily reduces hepatic glucose production and improves insulin sensitivity.
The boxed warning specifically addresses postmarketing cases of metformin-associated lactic acidosis. This condition is a known, serious risk associated with metformin, characterized by its often subtle onset and potential for severe outcomes. Other SGLT2 inhibitors like dapagliflozin and empagliflozin are also used for type 2 diabetes, sometimes in combination with metformin.
What this means
The addition of a boxed warning for metformin-associated lactic acidosis to the Invokamet XR label underscores the critical importance of clinician awareness regarding this severe adverse event. Healthcare providers prescribing Invokamet XR must be vigilant for symptoms such as malaise, myalgia, respiratory distress, somnolence, and abdominal pain, which can indicate the onset of lactic acidosis. Early diagnosis and prompt management are crucial, as the condition can progress rapidly and lead to serious consequences, including death. The warning emphasizes the need for careful patient selection, monitoring of renal function, and awareness of risk factors that can predispose patients to lactic acidosis.
Source
This label revision was issued by the FDA on 2026-07-09. The detailed warning information is available on dailymed.nlm.nih.gov, specifically within the product listing for Invokamet XR.