SGLT2 inhibitors, which are some of the newest diabetes drugs on the market, may increase the risk of a serious condition.
A new study concludes that these medications actually double the likelihood of developing diabetic ketoacidosis.
Because diabetes is becoming more prevalent in the United States, the hunt for new and more effective medication is in full flow.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are the most recent additions to the list of available medicines.
SGLT2 inhibitors reduce blood glucose levels by encouraging the kidneys to increase sugar excretion in urine.
These drugs are often given in combination with other diabetes medications, such as metformin and insulin.
The new class of drugs has become relatively popular, but the latest research finds that they could increase the risk of a serious diabetes-related complication.
Rare but dangerous
Diabetic ketoacidosis is relatively uncommon but potentially life-threatening.
It occurs when acids called ketones build up in the body, increasing the acidity of the blood, or when the body does not produce enough insulin.
When insulin is absent, glucose cannot enter cells and provide them with the energy they need.
Therefore, the body falls back on its secondary fuel source: fat. Ketones are byproducts of burning fat.
Symptoms of diabetic ketoacidosis include increased thirst, abdominal pain, nausea and vomiting, and confusion. It can also cause swelling in the brain, and, if left unchecked, can be fatal.
Although diabetic ketoacidosis is more likely to occur in people with type 1 diabetes, it does occasionally appear in individuals with type 2 diabetes.
Examining the interaction
The new study, carried out by Dr. Michael Fralick and a team from Brigham and Women’s Hospital in Boston, set out to examine the interaction, if any, between SGLT2 inhibitors and diabetic ketoacidosis.
The team’s findings were published today in the New England Journal of Medicine.
Fralick decided to investigate this relationship after one of his patients with type 2 diabetes showed up at the emergency room with symptoms of diabetic ketoacidosis.
As Fralick explains, “My best research projects come from my patients. Their experiences drive the questions I investigate.”
In April 2013, SGLT2 inhibitors came onto the market.
Clinical trial data showed that they were relatively safe for use by patients with type 2 diabetes.
However, in 2015, the Food and Drug Administration (FDA) issued a warning on this drug type following reports of increased rates of diabetic ketoacidosis.
What researchers discovered
The latest study used data from 40,000 patients and compared the outcomes of individuals taking SGLT2 inhibitors with patients taking a DPP4 inhibitor, which are diabetes drugs that help to maintain higher insulin levels by blocking a specific enzyme.
After 180 days, 26 patients taking the DPP4 inhibitor were diagnosed with diabetic ketoacidosis, compared with 55 individuals taking SGLT2 inhibitors, equating to more than double the risk.
However, it is important to note that diabetic ketoacidosis is still a rare consequence of diabetes, with or without SGLT2 inhibitor use.
The importance of these findings lies more in how doctors might approach treating patients with these types of symptoms.
Although the overall numbers of diabetic ketoacidosis cases are low, Fralick believes that the effect may be even larger than the study’s data show.
“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 explains. “That means that the risk of this side effect might actually be even higher than what we found due to misdiagnosis/under recording.”