The Jardiance warning on packaging may not sufficiently warn patients and doctors of a reportedly increased risk of amputation.

Jardiance is an SGLT2 inhibitor used to treat type-2 diabetes. The drug manages blood sugar levels by causing the patient to excrete excess glucose through the urine.

A 2017 study known as CANVAS reportedly found that patients on another SGLT2 inhibitor (Invokana) were at a twofold increased risk of low limb amputations when compared to the placebo group.

The FDA later required new warnings for Invokana to warn consumers of the risks associated with the drug. Jardiance warning labels and other SGLT2 inhibitors labels were not changed, as the CANVAS trial only examined Invokana.

The link uncovered by the CANVAS trial was addressed again in 2018 in a study by researchers from Karolinska University Hospital in Stockholm, Sweden. This study found that users of SGLT2 inhibitors like Jardiance had a higher incidence of lower leg amputation than did users of a different class of diabetes medications known as GLP1 receptor agonists.

“Our study adds to the data on the safety of these drugs by assessing the association between SGLT2 inhibitor use and serious adverse events in a substantially different population as compared to those included in the clinical trials, a population representative of routine clinical practice,” lead researcher Peter Ueda told TCTMD.

The Swedish study analyzed data from Swedish and Danish databases. Researchers compared 21,008 new users of SGLT2 inhibitors and 27,278 new users of GLP1 receptor agonists between 2013 and 2016. In the SGLT2 inhibitor group, 98 percent of patients were reportedly treated with either Jardiance or Farxiga, referenced in the study by their generic names empagliflozin and dapagliflozin.

After analyzing the database information, researchers reportedly found that there were 2.7 lower limb amputations per 1,000 patient years of SGLT2 treatment. In comparison, the GLP1 group reportedly experienced 1.1 amputations per 1,000 patient years of treatment.

It has been theorized that Jardiance and other SGLT2 inhibitors, which manage diabetes by processing blood sugar out through urine, may dehydrate patients and thereby decrease blood volume. With decreased blood volume, circulation problems may occur – decreasing the body’s wound healing ability.

This may cause diabetic patients, who are already at an increased risk for diabetic foot ulcers, to have more trouble healing ulcers and fighting off infections. If foot ulcers become infected, they may quickly progress to gangrene and need amputation to treat.

To help manage the risk of amputation from diabetic foot ulcer complications, Ueda recommends that doctors help patients with preventative foot care. This may help catch foot ulcers before infections become severe enough to require amputation.

“As for lower-limb amputation, our findings should lead to further emphasis on the importance of counseling patients on routine preventative foot care,” Ueda said to TCTMD. “Moreover, patients at high risk of amputation—for example, such as those with peripheral artery disease or foot ulcers—might be monitored more closely if SGLT2 inhibitors are used.”