SGLT2 Ketoacidosis Risk Extends Beyond Treatment Initiation

Ketoacidosis risk among adults with type 2 diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitors was highest shortly after initiation but persisted throughout follow-up, according to a Scandinavian cohort and nested case–control study published in The Lancet Diabetes & Endocrinology.

Investigators analyzed national registry data from Sweden, Denmark, and Norway, identifying 322,597 SGLT2 inhibitor treatment episodes among 282,282 patients. Mean age was 63 years, and 36.1% of treatment episodes involved women. During a median follow-up of 1.3 years, 1,452 ketoacidosis events occurred, corresponding to an incidence of 2.43 per 1,000 person-years.

Factors associated with higher odds of ketoacidosis included an HbA1c of at least 83 mmol/mol versus 52 mmol/mol or lower (odds ratio [OR], 15.37), malnutrition (OR, 10.54), previous ketoacidosis (OR, 10.40), and a body mass index below 20 kg/m² versus 20 to less than 25 kg/m² (OR, 9.98). Recent hypoglycemia was also associated with increased risk (OR, 5.22).

Infection was the most common precipitating or co-occurring event, occurring in 31.8% of cases and 6.1% of controls (OR, 7.60). Strong associations were also observed with alcohol intoxication, acute renal events, acute abdomen, stroke, and major surgery. Investigators cautioned that associations involving some transient exposures might have been overestimated because milder conditions could have been under-recorded among controls.

Exploratory analyses suggested that many identified associations were characteristic of patients with type 2 diabetes generally rather than specific to SGLT2 inhibitor use. One year after ketoacidosis, 25.1% of 842 patients remained on an SGLT2 inhibitor, while insulin use increased from 31.9% to 73.0%. The investigators concluded that ketoacidosis risk should be assessed throughout treatment and that patients should be instructed to pause therapy during acute illness and stress.

Source: Kadesjö E, Söderling J, Hviid A, et al. Ketoacidosis with SGLT2 inhibitors in routine clinical practice of type 2 diabetes: Scandinavian cohort and nested case–control study. Lancet Diabetes Endocrinol. Published online September 1, 2026. doi:10.1016/S2213-8587(26)00162-2