Study highlights risk groups for a severe side effect of diabetes treatment
Patients with type 2 diabetes who have high blood glucose levels, low body weight, or a history of ketoacidosis are at increased risk of developing this serious condition when treated with so-called SGLT2 inhibitors. A study led by researchers at Karolinska Institutet also shows that the risk persists throughout the entire course of treatment.
SGLT2 inhibitors are a class of medicines used to treat type 2 diabetes and can also reduce the risk of heart and kidney disease. At the same time, they are associated with an increased risk of ketoacidosis, a rare but serious condition in which a lack of insulin causes the body to produce large amounts of ketones. This can disrupt the body's acid–base balance and, in the worst cases, become life-threatening.
In the new study, published in The Lancet Diabetes & Endocrinology, researchers analysed national health registry data from Sweden, Denmark and Norway. The study included more than 280,000 patients with type 2 diabetes who had been treated with SGLT2 inhibitors. The researchers examined how often ketoacidosis occurred and which factors were associated with an increased risk.
Infection is a common trigger
The results showed that the risk was particularly high among patients who had previously experienced ketoacidosis, had high blood glucose levels, low body weight or signs of malnutrition. Previous episodes of hypoglycaemia were also associated with an increased risk. The researchers also found that infection was the most common triggering or co-occurring event in cases of ketoacidosis.
Other acute conditions, such as kidney impairment, stroke and major surgery, were also more common among affected patients. Previous studies have mainly examined the risk during the initial stages of treatment. The new study shows that although the risk is highest during the first few months, it remains elevated throughout the period in which the patient is taking the medication.
Provide clinicians with better support
“SGLT2 inhibitors provide medical benefits for many patients. Our findings are not primarily about avoiding treatment, but about improving our ability to identify high-risk patients and use these medicines more safely,” says Peter Ueda, MD, PhD, Assistant Professor at the Department of Medicine, Solna, Karolinska Institutet.
The researchers hope that the findings will provide clinicians with better support when making treatment decisions and help ensure that patients receive clearer advice on when the medication should be temporarily paused, for example during acute illness or before surgery. The next step is to study more closely the patients who develop ketoacidosis while receiving treatment and to investigate other rare but serious side effects of modern diabetes medicines.
The study was conducted in collaboration with the Statens Serum Institut in Denmark and the Norwegian University of Science and Technology (NTNU) in Norway. Funding was provided by Region Stockholm (ALF funding) and the Swedish Society of Medicine.
Publication
“Ketoacidosis with SGLT2 inhibitors in routine clinical practice of type 2 diabetes: Scandinavian cohort and nested case–control study”, Erik Kadesjö, Jonas Söderling, Anders Hviid, Viktor Wintzell, Henrik Svanström, Björn Eliasson, Soffia Gudbjornsdottir, Mads Melbye, Kristian Hveem, Christian Jonasson, Daniel P Andersson, Björn Pasternak, Peter Ueda, The Lancet Diabetes & Endocrinology, online 1 September 2026, doi: 10.1016/ S2213-8587(26)00162-2.