People taking a class of diabetes medications called SGLT2s have up to three times the risk for a serious complication called diabetic ketoacidosis (DKA) compared to people taking another drug, new research reveals.
SGLT2 (sodium-glucose cotransporter-2) inhibitors -- such as Farxiga, Jardiance and Invokana -- are a newer type of oral diabetes medicine. This class of medications is known to have many positive effects, including lowering a patient's risk of heart attack, heart failure, kidney disease and death from heart disease.
But several troubling side effects, including infections and a possible increased risk of DKA, have emerged.
"There was some uncertainty about how much the risk of DKA was, so we wanted to get a more precise estimate of the risk. We found a threefold increased risk," said senior author Kristian Filion. He's an investigator in clinical epidemiology at the Lady Davis Institute at Jewish General Hospital in Montreal, Canada.
"DKA appears to be a side effect of SGLT2s," he said. "It's an adverse effect that physicians need to be aware of, and alert their patients to."
SGLT2 inhibitors cause the kidneys to remove blood sugar through urination, which lowers overall blood sugar levels, according to the U.S. Food and Drug Administration.
Dr. Akankasha Goyal, an endocrinologist at NYU Langone Health in New York City, explained that when SGLT2s lower blood sugar levels, insulin production slows. Insulin is a hormone that is necessary for moving sugar from the blood into the body's cells.
If you don't have enough insulin to let your blood sugar fuel your cells, the body turns to stored fat for energy. A by-product of this process is ketones, according to the American Diabetes Association (ADA).
If ketones build up in the blood, it becomes more acidic and causes diabetic ketoacidosis, Goyal explained.
"DKA is a diabetic emergency. Someone in DKA needs to be hospitalized," she said. The condition is usually rare in people with type 2 diabetes because they usually make enough insulin to prevent it, she added.
Untreated, DKA can lead to death, the ADA said.
The new study included more than 200,000 people with type 2 diabetes who started using SGLT2 inhibitors between 2013 and 2018. They were compared to a matched group of people who took a different class of diabetes medications called DPP-4 inhibitors.
During the study, 521 people were diagnosed with DKA.
For people taking SGLT2 inhibitors, the risk of DKA was nearly three times higher, the study found. And, risk varied with the type of SGLT2 inhibitor used.
Dapagliflozin (Farxiga) was linked to an 86% increase in DKA risk, while patients using empagliflozin (Jardiance) had 2.5 times the risk of DKA compared to those on DPP-4s, the study found. Canagliflozin (Invokana) was associated with 3.6 times higher odds of DKA.
The good news, however, is that you can take steps to prevent DKA and get the benefits of SGLT2 inhibitors.
Goyal said the risk of DKA is highest when someone begins taking an SGLT2 inhibitor. Staying hydrated is a good way to help prevent it. It's also important to check with your diabetes doctor before taking any new medications. And, find out how often you should check your blood sugar levels.
She said it's also important to be aware of the DKA symptoms so you can seek treatment without delay if needed.
Symptoms include dry mouth, frequent thirst and urination, fatigue, nausea and vomiting, trouble concentrating and fruity-smelling breath, according to the ADA.
Goyal said SGLT2 inhibitors are a potent and effective class of medications.
"They really help with diabetes and heart failure, and can even help with cardiovascular risk in people who don't yet have heart disease," she said. "These medications are really good for people with kidney disease, too. And they're easy. One pill, once a day."
Filion said all drugs have benefits and risks that should be brought to patients' attention.
"These drugs have been shown to lower blood glucose levels and have benefits for the heart and kidneys. They also have some risks," he said. "Patients and physicians need to discuss the benefits and risks, particularly the risk factors for DKA."
The report was published online July 28 in the Annals of Internal Medicine.
Learn more about diabetic ketoacidosis from the American Diabetes Association.