Researchers who tracked more than 280,000 type 2 diabetes patients on SGLT2 inhibitors found that three patient traits stood out as red flags for ketoacidosis. High blood glucose, low body weight and a prior episode of ketoacidosis were each linked to a sharply elevated risk of the complication.
The findings, published September 1, 2026 in The Lancet Diabetes & Endocrinology, come from a Scandinavian cohort with a nested case-control analysis led by Karolinska Institutet, with Statens Serum Institut in Denmark and Norwegian University of Science and Technology.
The data cover more than 280,000 people prescribed SGLT2 inhibitors across Sweden, Denmark and Norway.
SGLT2 inhibitors, sold as Jardiance (empagliflozin), Farxiga (dapagliflozin), Invokana (canagliflozin) and Steglatro (ertugliflozin), are among the most widely used diabetes drug classes and also cut the risk of heart failure and chronic kidney disease.
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Ketoacidosis is a rare but serious side effect in which the body, short on insulin, produces dangerous amounts of ketones.
Why this side effect is easy to miss
Classic diabetic ketoacidosis usually announces itself with very high blood sugar. The SGLT2 version often does not.
It is known as euglycemic diabetic ketoacidosis, a condition in which blood glucose can look near normal, typically below 200 mg/dL, while blood chemistry tips into severe acidosis. That reassuring number on a home glucose monitor can throw both patients and clinicians off the scent.
The pattern has been on regulators' radar for a decade. In 2015 the U.S. Food and Drug Administration added warnings about ketoacidosis to the labels of Invokana, Farxiga and Jardiance after hospital cases mounted.
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The three factors that stood out
The Karolinska team singled out patients with:
- a previous episode of ketoacidosis
- elevated blood glucose before or during treatment
- low body weight or signs of malnutrition
Previous hypoglycemic episodes, infections, kidney impairment, stroke and major surgery also raised risk. Infection was the most common triggering event, the researchers noted.
The danger did not fade after the first weeks. Although risk peaks in the first months of treatment, it persists throughout the entire course of therapy, the team reported. That is a shift from earlier FDA case reports, which focused on the first two weeks after starting the drug.
In a statement from the university, Peter Ueda, assistant professor at the Department of Medicine, Solna, at Karolinska Institutet, said, "SGLT2 inhibitors provide medical benefits for many patients. Our findings are not primarily about avoiding treatment, but about improving our ability to identify high-risk patients and use these medicines more safely."
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Symptoms to know
The warning signs mirror classic ketoacidosis, minus the sky-high glucose reading. Nausea, vomiting, abdominal pain, unusual fatigue, difficulty breathing and confusion are the ones drug labels and diabetes specialists highlight. A fruity odor on the breath is another marker. Because blood sugar can look normal, a ketone test is the reliable check.
What to raise with your doctor
Patients on Jardiance, Farxiga or another SGLT2 inhibitor who fall into one of the highlighted groups can ask their prescriber how to monitor for ketoacidosis, particularly during illness, before planned surgery or if they sharply cut carbohydrates.
The Karolinska researchers stress that the point is safer prescribing, not blanket avoidance, given the drugs' proven benefits for heart and kidney outcomes.
Anyone who develops persistent nausea, vomiting or shortness of breath while on one of these medicines should seek medical attention and tell the clinician which drug they take. In an SGLT2 user, ketone testing is warranted even when the glucose meter reads normal.
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This article is made and published by Jesper Bengtson, who may have used AI in the preparation.