This Scandinavian cohort and nested case–control study used nationwide registry data from Sweden, Denmark, and Norway (2013–2022) to assess the incidence, risk factors, and prognosis of ketoacidosis in 282,282 adults with type 2 diabetes across 322,597 SGLT2 inhibitor treatment episodes.
Ketoacidosis occurred at 2.43 per 1,000 person-years (1,452 events; median follow-up 1.3 years). Strongest risk factors: high HbA1c ≥83 mmol/mol (OR 15.37), malnutrition (OR 10.54), prior ketoacidosis (OR 10.40), BMI <20 kg/m² (OR 9.98), and recent hypoglycaemia (OR 5.22). Infection was the most common precipitating event (31.8% of cases vs 6.1% of controls; OR 7.60). At 1 year post-ketoacidosis, only 25.1% of patients remained on SGLT2 inhibitors, while insulin use rose from 31.9% to 73.0%.
Associations for some transient exposures (e.g., milder illnesses) may be overestimated due to under-registration of these events among controls. Exploratory analyses suggest most risk factors are not SGLT2-inhibitor–specific but general to type 2 diabetes, limiting causal inference. Observational design precludes definitive causal conclusions.
Reassess ketoacidosis risk throughout SGLT2 inhibitor treatment—not just at initiation—especially in patients with high HbA1c, low BMI, malnutrition, or prior ketoacidosis. Counsel all patients to pause SGLT2 inhibitors during acute illness, surgery, or other physiological stress.
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