Persistent ketoacidosis risk found with SGLT2 diabetes drugs

A large Scandinavian observational study suggests that people with type 2 diabetes taking SGLT2 inhibitors remain at risk of ketoacidosis throughout treatment, not only soon after starting therapy. The study, published in *The Lancet Diabetes & Endocrinology*, examined 322,597 SGLT2 inhibitor treatment periods among 282,282 adults in Sweden, Denmark and Norway. Researchers recorded 1,452 ketoacidosis cases, equal to 2.43 cases per 1,000 person-years of treatment.

SGLT2 inhibitors such as dapagliflozin and empagliflozin help lower blood glucose by increasing glucose excretion in urine, and they have important cardiovascular and kidney benefits. But ketoacidosis is a serious, potentially life-threatening complication caused by a buildup of ketones in the blood. The study found that risk was highest during the first 180 days after starting an SGLT2 inhibitor, but it persisted during follow-up, which had a median duration of 1.3 years.

The risk varied sharply by patient characteristics and acute health events. Very high HbA1c was associated with more than 15 times the odds of ketoacidosis compared with the lowest HbA1c category. Malnutrition, prior ketoacidosis and BMI below 20 were each linked to roughly tenfold higher odds, while recent hypoglycemia was linked to more than fivefold higher odds. Infection was the most common associated acute event, appearing in 31.8% of ketoacidosis cases versus 6.1% of matched controls. The authors argue that risk assessment should continue during treatment, especially during illness, surgery or other physical stress, and that patients should be advised when temporary medication pauses may be appropriate.