Canagliflozin: Metformin boxed warning revised September 2026

On September 9, 2026, the FDA revised the boxed warning on the metformin label associated with the canagliflozin and metformin hydrochloride product listings. The warning concerns metformin-associated lactic acidosis and states that postmarketing cases have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias.

Background

Canagliflozin is listed in the supplied drug data alongside Invokana, Invokamet, Invokamet XR, canagliflozin and metformin hydrochloride, and metformin hydrochloride. The event itself concerns a revision to the metformin label rather than a clinical trial result or a new indication.

The revised warning identifies lactic acidosis associated with metformin as a postmarketing safety concern. The supplied FDA summary also states that the onset of metformin-associated lactic acidosis is often subtle, although the available text ends before providing the remainder of that statement.

What changed

The event was classified as an FDA label revision effective September 9, 2026. Its raw headline identifies the change as a revised boxed warning on the metformin label. The warning specifically describes serious outcomes reported in postmarketing cases, including death, low body temperature, low blood pressure, and persistent slow heart rhythms.

The supplied data do not provide additional prescribing instructions, risk-factor details, monitoring recommendations, dosing changes, contraindications, or evidence comparing canagliflozin-containing products with other treatments. They also do not state whether the revision changed the indication for canagliflozin or metformin.

What this means

The revision places metformin-associated lactic acidosis in the central safety warning for the affected metformin labeling. Clinicians, researchers, and patient advocates reviewing canagliflozin and metformin hydrochloride products should distinguish this safety-label event from evidence of efficacy or a new approval. The supplied information supports awareness of the serious postmarketing outcomes listed by FDA, but does not provide enough detail to assess their frequency, causes, or the effect of the label revision on treatment decisions.

Source

Source: U.S. Food and Drug Administration, DailyMed label document for the metformin-related product record, effective September 9, 2026. Available at dailymed.nlm.nih.gov.