Side Effects of Onglyza, Similar Diabetes Drugs More Likely To Cause Kidney Damage Than SGLT2 Inhibitors: Study

A recent study raised further questions about the potential risk of kidney damage linked to Invokana and other diabetes drugs from the same class, indicating that side effects of Onglyza and other older medications were more likely to cause problems.

Scandinavian researchers published a study last month in the medical journal The BMJ, suggesting diabetes drugs from a newer class of treatments known as sodium-glucose co-transporter 2 (SGLT2) inhibitors were less likely to cause serious kidney problems than other diabetes drugs on the market, like Onglyza.

That finding goes against some previous research, which led the FDA to require the makers of Invokana, Farxiga, Jardiance and other SGLT2 inhibitor diabetes drugs to add warnings about kidney side effects in 2016.

In this latest study, researchers from Sweden, Denmark and Norway conducted a cohort study using a nationwide registry, involving nearly 30,000 new SGLT2 Inhibitor users, and compared them to an identical number of new users of a class of diabetes drugs known as dipeptidyl peptidase-4 (dpp4) inhibitors, which includes Onglyza, Januvia, Galvus and Tradjenta.

The mean age of participants in the study was 61 years. Nearly 20% had heart disease, and about 3% had chronic kidney disease.

According to their findings, the use of Invokana and similar diabetes medications was linked to a reduced risk of serious kidney problems. Those taking SGLT2 inhibitors experienced 2.6 events per 1,000 person years. That compares to 6.2 events among Onglyza and Januvia users.

Compared to dpp4 users, those taking Invokana or Farxiga faced only about one third the risk of renal replacement therapy, 41% of the risk of being hospitalized for kidney problems, and only three quarters of the risk of death from renal causes.

“In this cohort study using nationwide registers in three countries, use of SGLT2 inhibitors was associated with a lower risk of the main composite outcome of serious renal events (consisting of renal replacement therapy, renal death, and hospital admission for renal events) in analyses using dipeptidyl peptidase-4 inhibitors as an active comparator,” the researchers determined. “Use of SGLT2 inhibitors was associated with a significantly lower risk of incident renal replacement therapy, as well as hospital admission for renal events, but not with death due to renal causes.”

The study is the second in less than a month to question kidney warnings on Invokana and similar drugs. Another study, published in early April by Canadian researchers, also concluded SGLT2 inhibitors were less likely than dpp4 inhibitors to cause kidney problems.

Invokana Health Concerns

Invokana (canagliflozin) was the first SGLT-2 inhibitor introduced to the market, which was approved in March 2013, and quickly became a blockbuster treatment. The new class of medications work in a unique way, impacting some normal kidney functions to help remove glucose from the body through urine. Similar drugs that are part of the same class include Invokamet, Invokamet XR, Farxiga, Xigduo XR, Qtern, Jardiance, Glyxambi, Synjardy, Synjardy XR, Steglatro, Segluromet and Steglujan.

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

The Canadian study determined last month that this warning was unnecessary.

Beyond kidney problems, Invokana and similar drugs have been linked to a number of other health problems in recent years.

In December 2015, the FDA required Johnson & Johnson to add new diabetic ketoacidosis warnings to Invokana and similar drugs, indicating that the medications increase the risk of this serious condition, which typically results in the need for emergency treatment to avoid life-threatening injury. Prior to the update, the warnings failed to alert consumers about the importance of seeking immediate medical attention if they experience symptoms like abdominal pain, fatigue, nausea, respiratory problems or vomiting.

In May 2017, FDA required new warnings about the Invokana amputation risks, adding information to the drug label about the increased incidence of leg, foot and toe amputations. The 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.

In addition, in August 2018 the FDA issued a warning linking the drugs to serious flesh-eating infections around the genitals, known as necrotizing fasciitis of the perineum, or Fournier’s gangrene.

Johnson & Johnson and Janssen have faced several thousand other Invokana lawsuits, which allege users and the medical community were not provided adequate warnings at the time the drug was first introduced. The makers of other diabetes drugs from the same class, including Farxiga and Xigduo XR, have also faced similar lawsuits; though most have been filed against the makers of Invokana.