09 June 2017

New diabetes meds linked to life-threatening complication

A study found that SLGT2 inhibitors can increase the risk for a dangerous condition known as diabetic ketoacidosis.


A new class of type 2 diabetes drugs called SGLT2 inhibitors could increase the risk of a rare, life-threatening complication of the disease called ketoacidosis, a new study warns.

SGLT2 inhibitors include prescription medications such as canagliflozin, dapagliflozin and empagliflozin. Brand names are Invokana, Invokamet, Farxiga, Xigduo XR, Jardiance and Glyxambi. (A previous Health24 article reported on dapagliflozin.)

Uncommon in type 2 diabetics

These drugs first became available in 2013, but in 2015 the US Food and Drug Administration (FDA) issued a warning about an increased risk for diabetic ketoacidosis when SGLT2 inhibitors are used.

The condition typically occurs in people with type 1 diabetes. And while it is uncommon in people with type 2 diabetes, case reports have shown it can occur with type 2 disease, according to the study authors.

Ketoacidosis can cause:

  • Vomiting
  • Abdominal pain
  • Shortness of breath 
  • Swelling in the brain

Left untreated, the condition can be fatal, the researchers said.

The new study "essentially confirms what doctors had already suspected," said diabetes expert Dr Stanislaw Klek, an endocrinologist at NYU Winthrop Hospital in Mineola, New York

"Fortunately, the rate of diabetic ketoacidosis is still very low and should not prevent the usage of this medication class," he added. "It is important to be aware of this potential complication and monitor for symptoms of diabetic ketoacidosis, particularly during periods of illness."

Risk remains slim

In the new study, researchers at Brigham and Women's Hospital in Boston analysed data from 40 000 people with type 2 diabetes. They found that those taking SGLT2 inhibitors were twice as likely to develop diabetic ketoacidosis than those taking another class of diabetes drugs called DPP4 inhibitors (drugs such as Januvia and Onglyza).

Diabetic ketoacidosis is a complication of diabetes and develops when the blood becomes more acidic than body tissues due to low insulin levels.

Still, the risk to any one patient remains very slim, the researchers stressed. They estimated that among patients taking an SGLT2 inhibitor, only about 1 in every 1 000 patients would develop this ketoacidosis.

The findings were published in the New England Journal of Medicine.

Even though diabetic ketoacidosis is uncommon, doctors need to closely monitor type 2 diabetes patients for signs and symptoms of the complication, said study author Dr Michael Fralick. He's from Brigham and Women's division of pharmacoepidemiology and pharmacoeconomics.


"This is a side effect that's usually seen in patients with type 1 diabetes mellitus – not type 2 – so doctors are not 'on the lookout' for it," Fralick said in a hospital news release. "That means that the risk of this side effect might actually be even higher than what we found due to misdiagnosis/under-recording."

Rise in ketones

Dr Minisha Sood is an endocrinologist at Lenox Hill Hospital in New York City. Reviewing the findings, she explained that SGLT2 inhibitors "have been a welcome addition to the arsenal of glucose [blood sugar]-lowering medications. They lower blood glucose by increasing the amount of glucose eliminated through the urine."

But the drugs may interfere with levels of a particular hormone, glucagon, which in turn leads to an unhealthy rise in acids called ketones. "When ketone acids build up in the system, this can lead to diabetic ketoacidosis," Sood explained.

She agreed that patients and doctors should be alert to the rare but potential risk for diabetic ketoacidosis, especially in the early weeks after a person starts taking an SLGT2 inhibitor.

But Sood believes the study findings are not reason for patients to immediately switch to another form of diabetes medication.

"SLGT2 inhibitors work extremely well to control diabetes [and they have the added benefit of lowering blood pressure and weight as well] so the benefits definitely outweigh the risks of therapy," she said.

Read more:

Older diabetes meds as good

More type 1 diabetes kids face dangerous complications

Diabetes: hypoglycaemia and hyperglycamia


Ask the Expert

Diabetes expert

Dr. May currently works as a fulltime endocrinologist and has been in private practice since 2004. He has a variety of interests, predominantly obesity and diabetes, but also sees patients with osteoporosis, thyroid disorders, men's health disorders, pituitary and adrenal disorders, polycystic ovaries, and disorders of growth. He is a leading member of several obesity and diabetes societies and runs a trial centre for new drugs.

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