Although regulatory action made changes to Jardiance prescribing information, previous patients may not have been warned of the drug’s amputation risks.

In late 2018, a study, reported on WebMD, by researchers at Karolinska University Hospital in Stockholm, Sweden revealed that certain medications in a drug class of type-2 diabetes may increase the risk of a leg or foot amputation. The drugs affected are part of the SGLT-2 inhibitor drug class, which includes Jardiance, Farxiga, and more.

These medications work by eliminating excess sugar in the blood by increasing urination – the body’s natural mechanism for disposing of excess sugar. This mechanism may or may not be involved in the drug class’ increased risk of leg and foot amputations.

In 2017, the U.S. Food and Drug Administration (FDA) issued a safety warning to inform the public that two large clinical trials linked canagliflozin, the active ingredient in other SGLT2 inhibitor medication including Invokana and Invokamet, with an increased risk of leg and foot amputation. The alert resulted in new warnings regarding Invokana amputation risks on drug packaging.

The new study from Karolinska University Hospital has expanded the link to include dapagliflozin (Farxiga) and empagliflozin (Jardiance). In the observational study, researchers analyzed the outcomes of 17,213 SGLT-2 inhibitor patients with those of 17,213 GLP-1 receptor agonist patients between July 2003 and December 2016. In the SGLT-2 inhibitor population, 61 percent of patients were on Farxiga, 38 percent were on Jardiance, and 1 percent were on canagliflozin medications.

The results showed that SGLT-2 inhibitors were associated with a twofold increased risk of amputation. In the absence of FDA action, it is unclear whether or not changes with made to Jardiance prescribing information, but consumers on the medication and prescribing doctors may want to consider amputation risk factors when prescribing SGLT-2 inhibitors.

“Patients at high risk of amputation, for example those with peripheral artery disease or foot ulcers, might be monitored more closely if SGLT2 inhibitors are used, and the risk of this adverse event may be considered when deciding on which drugs to use,” said lead researcher Dr. Peter Ueda, according to WebMD.

The study also showed a twofold increased risk of ketoacidosis, a condition already warned about in Jardiance prescribing information. Ketoacidosis is the condition of increased ketones (acids) in the blood which can be life threatening. Symptoms of ketoacidosis may include nausea, vomiting, abdominal pain, fatigue, and breathing problems.

Although the results of this study may be the first of many to explore the link between SGLT-2 inhibitors and amputations, some doctors are unconvinced by the results of the observational study. These individuals note that the study was observational, not clinical, so the results may not as reliable as clinical study results.

“They’re reporting an increased risk that hasn’t been observed in prospective, randomized, placebo-controlled trials, and that’s the gold standard,” said Dr. Kevin Pantalone, an endocrinologist at the Cleveland Clinic, speaking to WebMD. “Yes, it’s interesting they find this observation in patients who are on SGLT2 inhibitors, but only 1 percent of the patients were on the drug that is really concerning for harm.”

Further study is likely required before a definitive conclusion can be reached, but consumers may want to be mindful of the observational study’s results.