Study Finds Ketoacidosis Risks from Side Effects of Invokana, Jardiance, Similar Diabetes Drugs

Side effects also included a lower risk of acute kidney injury and death, in addition to the potential dangers.

A class of diabetes drugs that includes Januvia and Invokana, appear to reduce the risk of death and acute kidney injury for type 2 diabetics after undergoing surgery.

However, according to findings published in JAMA Surgery late last month, researchers have also found the medications, known as sodium-glucose cotransporter-2 (SGLT-2) inhibitors or gliflozins, appeared to increase the risk of a type of diabetic ketoacidosis that can occur when blood sugar levels are normal.

Diabetic ketoacidosis (DKA) usually occurs when high levels of blood acids, known as ketones, build up in the body. This can result in symptoms like difficulty breathing, nausea, vomiting, abdominal pain, confusion, fatigue or sleepiness, often requiring hospitalization, urgent medical treatment, and potentially resulting in severe health consequences.

However, in euglycemic diabetic ketoacidosis (eKA), the blood sugar levels appear to be normal, which could result in a misdiagnosis, delayed treatment and life-threatening complications.

In the new study, a research team from the University of California, San Francisco sought to verify several case reports and small retrospective studies, which appeared to indicate that drugs like Invokana and Januvia could increase the risk of eKA and acute kidney injury (AKI) after surgery.

The researchers, led by Dr. Roberta Teixeira Tallarico, looked at data on nearly half a million patients undergoing surgery from January 1, 2014 to December 31, 2022. They selected 7,439 SGLT2 patients, and compared them with 33,489 control patients.

According to their data, patients who took drugs like Januvia and Farxiga before surgery saw an 11% increased risk of eKA when compared to those who did not. However, the researchers also found that those same medications appeared to decrease the risk of postoperative acute kidney injury after surgery by 30% and decreased the risk of death significantly. During the 30-day period after surgery, those who had taken the drugs regularly had a 1.1% mortality rate, compared to a 1.5% chance of death for those who did not take the drugs.

The researchers found that those patients who did suffer diabetic ketoacidosis were hospitalized twice as long on average, six days, when compared to those who did not suffer eKA, who went home in three days.

“In this retrospective matched case-control study, patients treated with SGLT2i had a slightly but statistically significantly higher risk of postoperative eKA compared with control patients,” the team concluded. “It also showed a lower risk of AKI and 30-day mortality.”

Invokana Lawsuits

Invokana was the first of the SGLT2 class of medications introduced to the market in 2013. However, manufacturers were required by the FDA to update the warning labels and prescribing guides several times, as Invokana and similar drugs were linked to a growing number of side effects.

The FDA first required additional label warnings about a link between kidney risks and Invokana, as well as other drugs from its class in June 2016, indicating the medications may increase the risk of acute kidney injury and other severe health problems.

In May 2017, federal officials required makers of Invokana to specifically add warnings about amputation risks, including information on the drug label about the increased incidence of leg, foot and toe amputations. That warning was only required for Invokana, and manufacturers of other SGLT-2 inhibitors have suggested that Invokana leg and foot amputation problems were unique to that drug, maintaining that the same risks were not seen among users of their medications.

A drug safety communication was then issued by the FDA in August 2018, about the risk of Fournier’s gangrene from Invokana, Invokamet and similar diabetes drugs. Incidents of the serious genital infections, also known as necrotizing fasciitis of the perineum, can result in the disintegration of flesh and can be life-threatening.

Following several years of litigation, Johnson & Johnson and Janssen have reached Invokana settlements to resolve most of the litigation.