A widely prescribed class of medications for type 2 diabetes may increase the risk of a life-threatening condition known as ketoacidosis, or a "diabetic attack," according to new research. Swedish scientists have warned that SGLT2 inhibitors, taken by millions globally, could trigger the buildup of harmful ketones in the blood, leading to severe complications.
The study, published in The Lancet Diabetes and Endocrinology, analyzed health records of nearly 280,000 individuals with type 2 diabetes who were treated with SGLT2 inhibitors. These drugs, which include brand names such as Forxiga, Invokana, Jardiance, and Steglatro, help lower blood sugar by increasing the amount of sugar excreted through urine. They are also prescribed for their benefits in protecting against heart failure and kidney disease, and some have been associated with weight loss.
Researchers from the Karolinska Institute found that the risk of ketoacidosis was higher in patients who had a history of the condition, had high blood sugar levels, were underweight, or showed signs of malnutrition. Individuals with a history of dangerously low blood sugar, or hypoglycemia, were also identified as high-risk.
While infections were noted as the most common trigger for ketoacidosis overall, the study highlights that SGLT2 inhibitors may act as a trigger for these vulnerable patients. The risk, though most pronounced in the initial months of treatment, was found to persist throughout the duration of drug use. Previous research had largely focused on the early stages of treatment.
"SGLT2 inhibitors provide medical benefits for many patients," said Peter Ueda, assistant professor at the Karolinska Institute. "Our findings are not primarily about avoiding treatment, but about improving our ability to identify high-risk patients and use these medicines more safely." The researchers aim for their findings to assist physicians in determining when to stop treatment and plan further investigations into other rare but serious side effects of modern diabetes medications.
This warning follows separate research indicating a rise in ketoacidosis deaths in the UK. A study from Imperial College London reported an 81 percent increase in ketoacidosis cases between 2015 and 2023. Symptoms of ketoacidosis can include excessive thirst, frequent urination, stomach pain, nausea, vomiting, diarrhea, blurry vision, rapid breathing, a fruity-smelling breath, and extreme fatigue or confusion.
Approximately 10 percent of individuals with type 2 diabetes have a body mass index that falls outside the overweight or obesity categories, according to Diabetes UK. Experts have previously theorized that SGLT2 inhibitors may prompt the body to burn fat for energy, which in turn can lead to increased ketone production.