Farxiga amputation risk may increase if a patient taking the sodium glucose cotransporter 2 (SGLT2) inhibitor has a current foot ulcer, a diagnosis of peripheral artery disease (PAD) or a previous history of diabetes related amputation.

While previously only Invokana and Invokamet—SGLT2 inhibitors containing canagliflozin—had a known link to an increased risk of amputation, Consumer Healthday indicates that a new study is implicating the whole medication class.

The two large clinical trials that led to the 2017 FDA amputation warning linked the ingredient in Invokana and Invokamet with this disfiguring adverse side effect. Jardiance and Farxiga amputation risk had not yet been pinpointed.

Jardiance and Farxiga are known generically as empagliflozin and dapagliflozin, respectively. The new observational study that has identified Jardiance and Farxiga amputation risk is not a prospective, randomized, placebo-controlled trial, according to Dr. Kevin Pantalone—a doctor quoted by Consumer Healthday.

Nevertheless, the fact that it was found when only one percent of the study participants were taking the previously-identified problematic SGLT2 inhibitor is a significant finding.

Parameters of Study and How SGLT2 Inhibitors Work

The new study took data from 17,213 patients taking SGLT2 inhibitors and 17,213 patients taking GLP1 receptor agonists between a recent 13-year time period in Denmark and Sweden.

The study showed that Jardiance and Farxiga amputation risk, as well as that of other SGLT2 inhibitors, was nearly double that of patients taking GLP1 receptor agonists. Despite attempts to exert many controls on this analysis, it was incapable of proving that this medication class causes the risk of amputation risk to rise by itself.

SGLT2 inhibitors work by stopping the kidneys from sending a type-2 diabetic’s extra blood glucose back to the bloodstream for re-absorption. Rather, the extra sugars are allowed to be expelled from the body through its urine output. It can be a very effective mechanism, but one that can produce dehydration very quickly if the patient is not religiously maintaining their fluid intake.

In a dehydrated state, problems such as PAD can become worsened. According to the Mayo Clinic, PAD involves a buildup of fatty deposits in the arteries that supply blood to the lower extremities.

The constriction can cause pain and cramping with walking and less blood volume due to poor fluid intake can increase this symptom. The underlying reality is that tissues are literally crying out for oxygenation and nutrition they are not getting. One of the major risk factors for this condition is type-2 diabetes for which a SGLT2 inhibitor would be prescribed.

Foot ulceration often goes hand-in-hand with PAD and are also a problem often related to the high blood sugars present in a diabetic. According to Healthline, poor circulation from PAD can cause literal tissue death which in an advanced state would require amputation in order to protect healthy tissue.

The take away from this new study might be that with patients already suffering from PAD or foot ulceration, SGLT2 inhibitors might not be the best choice of treatment by the physician or patient.