SGLT2 Inhibitors: Study Identifies Risk Groups for Severe Side Effects

Large Study Links SGLT2 Inhibitors to Ketoacidosis Risk in Type 2 Diabetes

Researchers from Karolinska Institutet analyzed health registry data from Sweden, Denmark, and Norway to study the risk of ketoacidosis in over 280,000 patients with type 2 diabetes treated with SGLT2 inhibitors.

SGLT2 inhibitors are used to manage blood sugar and reduce heart and kidney disease risk in type 2 diabetes, but they can also increase the risk of ketoacidosis, a rare but potentially life-threatening condition.

Key Risk Factors Identified in the Study

The study found that patients with a history of ketoacidosis, high blood glucose levels, low body weight, or signs of malnutrition were more likely to develop ketoacidosis while taking SGLT2 inhibitors.

Previous episodes of hypoglycemia also increased risk. Infection was the most common trigger or co-occurring event in cases of ketoacidosis, and other acute conditions like kidney impairment, stroke, and major surgery were more common among affected patients.

• History of ketoacidosis
• High blood glucose
• Low body weight or malnutrition
• Previous hypoglycemia
• Acute illness or infection

Implications for Metabolic Health and Clinical Practice

The risk of ketoacidosis is highest during the first few months of SGLT2 inhibitor treatment but remains elevated throughout the entire course of therapy.

Researchers recommend that clinicians use these findings to better identify high-risk patients and provide clearer advice on when to temporarily pause SGLT2 inhibitors, such as during acute illness or before surgery.

Study Design, Limitations, and Next Steps

This was a large cohort and nested case–control study using national health registry data from three Scandinavian countries, published in The Lancet Diabetes & Endocrinology.

While the study provides new insights into risk factors for ketoacidosis with SGLT2 inhibitors, it does not address all possible rare side effects or individual patient circumstances. Further research is planned to study other serious side effects and to examine patients who develop ketoacidosis during treatment.