When the diabetes drug Invokana first hit the market in 2013, it was heralded as a breakthrough for patients who wanted to lower their blood sugar and possibly lose some weight too. But now, many of those hopeful patients are also wondering why does Invokana cause amputations.

Invokana, the trade name for the drug canagliflozin, is prescribed to patients for the treatment of type 2 diabetes. The drug is licensed from Mitsubishi Tanabe Pharma Corporation to Johnson & Johnson’s Janssen Pharmaceuticals division for distribution throughout most of the world.

According to the company, Invokana is proven to lower blood sugar (A1C) and the 300-mg dose is proven to reduce A1C levels lower than a competing drug from Merck called Januvia.

Invokana side effects include ketoacidosis, kidney problems, urinary tract infections, low blood sugar and a higher risk of broken bones.

But, earlier this year, the U.S. Food and Drug Administration began requiring new ‘black box’ warnings to be added to Invokana labels to describe the increased risk of leg and foot amputations to patients.

The FDA acted following two large clinical trials in which the data demonstrated that leg and foot amputations occurred about twice as often in patients treated with canagliflozin compared to patients treated with a placebo.

During the clinical trials, the researchers found that patients most often experienced amputations of the toe and middle of the foot. But, some patients had amputations involving the leg, below and above the knee. In addition, some patients had more than one amputation and some had both limbs amputated.

The trials did not answer the question of why does Invokana cause amputations. According to an article in Forbes recently, some doctors speculate that while the drug decreases blood sugar and blood pressure, it may also cause the blood to thicken and subsequently pool in the foot.

As researchers struggle to explain why the amputations occur, the FDA did make a note of which types of patients might be predisposed to amputation if they decide to take Invokana. The factors that appeared to increase the odds of amputation included a prior history of amputation, peripheral vascular disease, neuropathy and diabetic foot ulcers.