Invokana, a diabetes drug manufactured by Jannsen Pharmaceuticals, a Johnson & Johnson subsidiary, no longer requires a warning on the box that alerts users to the risk of amputation. 

The warning had been on Invokana boxes since 2017. But after the FDA reviewed data from three clinical trials, the agency determined that the risk of leg and foot amputation was lower than previously thought. Invokana (canagliflozin) received additional approval in 2018 to reduce the risk of major heart-related events such as heart attack, stroke, or death in patients with type 2 diabetes who have known heart disease, according to an FDA memo. This made Invokana the only oral type 2 diabetes treatment indicated to reduce the risk of heart attack, stroke or cardiovascular death. (Jardiance, another popular SGLT2 inhibitor, became the first diabetes drug to add a cardiovascular-death-risk-lowering benefit to its label.)

Additionally, last year, Invokana also received approval to reduce the risk of end-stage kidney disease, worsening of kidney function, heart-related death, and being hospitalized for heart failure in certain patients with type 2 diabetes and diabetic kidney disease, per the FDA memo. 

The agency noted that the risk of amputation was far outweighed by the benefits, especially now that the drug can also be beneficial for the heart and kidneys. 

Despite the removal of the warning on the box, the amputation risk will still be listed on the Warnings and Precautions section. 

In 2013, Invokana became the first so-called SGLT2 inhibitor drug to receive FDA approval. SGLT2 inhibitors reduce blood sugar levels by blocking the action of a protein (sodium-glucose co-transporter-2; SGLT2) in the kidney. Through this mechanism, the kidney does not reabsorb glucose from urine; the urine removes the glucose, thereby lowering the level of blood glucose.

Although the FDA box-warning removal is welcome news for J & J and Janssen, Fierce Pharma reports that sales of the drug have plunged by nearly half. In 2016, the year before the box warning was mandated, Invokana earned over $1.4 billion in sales. Last year, the figure was $735 million. Increased competition is also to blame for the steep revenue decline.