New Class of Diabetes Drugs Subject of FDA Warning

Less than two weeks ago, the FDA released an important drug safety communication regarding a new class of diabetes drugs, including those marketed under the brand names Invokana, Farxiga and Jardiance. Health regulators caution that diabetic patients taking this class of sodium-glucose cotransporter-2 (SGLT2) inhibitors may be at risk for extremely high levels of blood acids – a condition known as ketoacidosis – that could require hospitalization.

The diabetes medications have been widely prescribed because in addition to regulating blood glucose levels, they also encourage lower blood pressure and better weight management. Some of the older diabetes drugs could lead to weight gain, a problem considering obesity is one of the main causes of the condition.

The oral medications, which are FDA-approved to treat adult type II diabetes, function by triggering blood glucose to be secreted in the urine. The SGLT2 inhibitors include J&J’s Invokana (canagliflozin), Boehringer and Eli Lilly’s Jardiance (embagliflozin) and AstraZeneca’s Farxiga (dapagliflozin).

FDA diabetes drug warning

According to the agency’s drug safety communication, released May 15, 2015, diabetic patients who experience nausea, vomiting, confusion, impaired breathing, stomach pain or unusual sleepiness should seek prompt medical attention as these are potential symptoms of ketoacidosis. Healthcare providers can then evaluate patients for the presence of high acid blood levels and advise on whether SGLT2 inhibitors should be immediately discontinued.

Between March 2013 and June 2014 the FDA’s Adverse Event Reporting System database logged 20 incidents of acidosis reported as diabetic ketoacidosis (DKA) or ketosis in patients who were taking Farxiga, Invokana or Jardiance. All were rushed to the emergency room and needed hospital care to treat the condition. Health regulators have continued to receive adverse event reports regarding SGLT2 inhibitors and diabetic ketoacidosis since June of 2014.

DKA is a form of acidosis that is typically associated with type 1 diabetes and patients with dangerously high blood sugar levels. The adverse event reports were atypical for DKA because most of the patients suffered from type 2 diabetes and only had moderate increases in blood sugar levels.

SGLT2 inhibitors include:

• Invokana (canagliflozin)
• Invokamet (canagliflozin and metformin)
• Farxiga (dapagliflozin)
• Xigduo XR (dapagliflozin and metformin extended-release)
• Jardiance (empagliflozin)
• Glyxambi (empagliflozin and linagliptin)

Invokana and renal toxicity

The Institute for Safe Medication Practices (ISMP) cautions that initial adverse event reports for Invokana raises valid concerns about the drug’s inherent safety. During its first year on the market, Invokana was the topic of 457 serious adverse event reports, including 5 adverse outcomes related to the renal toxicity of Invokana.

These adverse effects linked to Invokana included:

• Fluid imbalances
• Kidney failure or impairment
• Kidney stones
• Abnormal weight loss
• Urinary tract infections

Furthermore, the ISMP tracked other adverse reports that suggest Invokana was the culprit behind:

• Urogenital fungal infections
• Skin rashes
• Uticaria
• Sudden swelling of the tongue, lips and throat

For the time being, the FDA urges medical providers and their patients to report adverse side effects connected to SGLT2 inhibitors to the agency’s MedWatch program, so further investigations may be conducted.

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