Ketoacidosis Risk Persists During SGLT2 Inhibitor Use

KETOACIDOSIS risk among people with Type 2 diabetes taking SGLT-2 inhibitors can persist throughout treatment and varies substantially according to individual patient characteristics, a large Scandinavian study has found.

High HbA1c, malnutrition, previous ketoacidosis, low BMI, and recent hypoglycaemia were among the strongest factors associated with increased risk.

More Than 320,000 Treatment Episodes

Researchers used nationwide health registers from Sweden, Denmark, and Norway to examine 322,597 episodes of SGLT-2 inhibitor treatment among 282,282 adults with Type 2 diabetes.

During a median follow-up of 1.3 years, 1,452 ketoacidosis events occurred, corresponding to an incidence of 2.43 events per 1,000 person-years.

Although the incidence was highest shortly after SGLT-2 inhibitor treatment began, the risk persisted throughout follow-up.

Major Risk Factors Identified

Poor glycaemic control emerged as one of the strongest risk markers.

Patients with HbA1c of at least 83 mmol/mol had more than 15-times the odds of ketoacidosis compared with those with levels of 52 mmol/mol or lower.

Malnutrition was associated with more than 10-times the odds, as was a previous history of ketoacidosis. A BMI below 20 kg/m² was associated with almost 10-times the odds compared with a BMI between 20 and less than 25 kg/m².

Recent hypoglycaemia was associated with more than five-times the odds of ketoacidosis.

Infection was the most common precipitating or co-occurring event, occurring in 31.8% of ketoacidosis cases compared with 6.1% of controls.

Risk Continues Beyond Treatment Initiation

The findings challenge the idea that ketoacidosis is primarily an early-treatment concern.

Although the complication remained uncommon overall, the researchers argue that risk assessment should continue for as long as patients receive SGLT-2 inhibitors.

Following ketoacidosis, treatment patterns also changed substantially. Among patients with available 1-year follow-up, insulin use increased from 31.9% to 73.0%, while approximately one-quarter remained on an SGLT-2 inhibitor.

The authors emphasise the importance of identifying high-risk patients and advising people taking SGLT-2 inhibitors to temporarily pause treatment during periods of acute illness or physiological stress.

Reference

Kadesjö E et al. Ketoacidosis with SGLT-2 inhibitors in routine clinical practice of type 2 diabetes: Scandinavian cohort and nested case-control study. Lancet Diabetes Endocrinol. 2026. doi:10.1016/S2213-8587(26)00162-2.