A class of medicines used for type 2 diabetes that also reduces risk of heart and kidney disease. They carry a rare but serious side effect: ketoacidosis — where lack of insulin leads to high ketone production, disrupting the body’s acid-base balance and potentially becoming life-threatening.
What the study did:
Published in The Lancet Diabetes & Endocrinology, researchers analyzed national health registry data from Sweden, Denmark and Norway. It included more than 280,000 patients with type 2 diabetes treated with SGLT2 inhibitors, looking at how often ketoacidosis occurred and what factors increased risk. Collaboration with Statens Serum Institut (Denmark) and NTNU (Norway).
Key findings on who is at higher risk:
- Highest risk factors: history of previous ketoacidosis, high blood glucose levels, low body weight or signs of malnutrition
- Also linked to higher risk: previous episodes of hypoglycaemia (low blood sugar)
- Most common trigger: infection was the most common triggering or co-occurring event when ketoacidosis happened
- Other acute conditions were more common in affected patients, including kidney impairment, stroke, and major surgery
Timing of risk:
Previous studies focused on the early months of treatment. This study found risk is highest in the first few months, but remains elevated throughout the entire time a patient is on the medication.
What it means for clinical care:
Lead author Peter Ueda, Assistant Professor at Department of Medicine, Solna, Karolinska Institutet, said the goal is not to avoid treatment — SGLT2 inhibitors benefit many patients — but to better identify high-risk patients and use the drugs more safely.
Researchers hope the findings help clinicians with treatment decisions and with guidance on when to temporarily pause the medication, for example during acute illness or before surgery.
Next steps are to study in more detail the patients who do develop ketoacidosis on treatment, and to investigate other rare but serious side effects of modern diabetes medicines.