FDA Warns of Amputation Risk With Antidiabetic Agent

New warnings, including a Boxed Warning, will be added to canagliflozin and canagliflozin-containing drug labels
New warnings, including a Boxed Warning, will be added to canagliflozin and canagliflozin-containing drug labels

The Food and Drug Administration (FDA) has concluded that canagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, carries an increased risk for leg and foot amputations. As a result, the FDA is requiring new warnings, including a Boxed Warning, to be added to canagliflozin and canagliflozin-containing drug labels to address this risk. 

Canagliflozin is an antidiabetic medication used with diet and exercise to improve glycemic control in adults with type 2 diabetes. By inhibiting SGLT2, canagliflozin reduces reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. 

The FDA's decision was based on new study data from the CANVAS (Canagliflozin Cardiovascular Assessment Study) and CANVAS-R (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus) trials. The data showed that the incidence of leg and foot amputations occurred about twice as often in canagliflozin-treated patients vs. placebo patients.  

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In the CANVAS study, the risk of amputations was 5.9 per 1,000 patients per year in the canagliflozin group vs. 2.8 per 1,000 patients per year in the placebo group (hazard ratio [HR] 2.12, 95% CI: 1.34, 3.38). In the CANVAS-R study, the risk of amputations was 7.5 per 1,000 patients per year in the canagliflozin group vs. 4.2 per 1,000 patients per year in the placebo group (HR 1.80, 95% CI: 1.10, 2.93). The most common amputations were of the toe and mid-foot (99/140); amputations involving the leg, below, and above the knee also occurred. were The most common precipitating medical events leading to amputation were lower limb infections, gangrene, diabetic foot ulcers, and ischemia. Patients with a baseline history of prior amputation, peripheral vascular disease, and neuropathy were found to be at greatest risk; clinicians should consider these risk factors prior to initiating treatment with canagliflozin. 

Canagliflozin is available as a single-ingredient drug as well as in combination with metformin. Healthcare professionals and patients can report adverse effects related to canagliflozin and other medicines to the FDA MedWatch program.

For more information visit FDA.gov.