A new study entitled “Postoperative Outcomes Among Sodium-Glucose Cotransporter 2 Inhibitor Users” published in JAMA Surgery calls into question the current guidelines advising doctors to pause a widely used class of diabetes drugs—sodium-glucose cotransporter 2 inhibitors (SGLT2i) — before surgery. The findings suggest the risk of developing postoperative euglycemic ketoacidosis (eKA), a serious and potentially life-threatening complication, slightly increased both in elective and emergent surgery, which challenges the current reccommendtion that stopping this medication prevent this risk.
SGLT2i , such as canagliflozin, dapagliflozin, and empagliflozin, have become popular treatments for type 2 diabetes in recent years, thanks to their benefits for both cardiovascular and kidney health. But use of these medications before surgery has been controversial due to a known, though rare, risk of triggering eKA—where a patient develops dangerous levels of ketones in the blood without the high blood sugar usually seen with eKA.
As a precaution, the U.S. Food and Drug Administration recommends stopping these medications at least three days prior to elective surgery. However, this new retrospective case-control study, which analyzed data from over 460,000 patients aged 18 years who underwent surgeries, found that the risk of eKA is modelty increased bith in emergent and elective surgeries.
“We found a statistically significant increase in postoperative eDKA risk among SGLT2 inhibitor users — albeit modest — which was associated with prolonged hospital length of stay. This risk was present both in elective and emergent procedures even though they likely did not stop the medication,” said Matthieu Legrand, MD, PhD, principal investigator at University of California, San Francisco, lead author of the study.
The research team examined surgical outcomes from the Veterans Affairs Health Care System (VAHCS) National Registry database between 2014 and 2022. Adult patients using SGLT2i, who underwent inpatient surgical procedures, such as plastic, cardiac, and orthopedic surgeries, were compared with a 1:5 matched control group that included such indicators as the patient’s demographic characteristics, comorbidities, and surgical characteristics. The researchers defined long-term SGLT2i use as having more than three fills of outpatient prescription or less than a 180-day gap of the last fill, according to the VAHCS pharmacy registries. They found that the risk of perioperative eKA was 11% higher for patients using SGLT2i than their matched counterparts. However, there was a 31% reduction in postoperative acute kidney injury an a 30% reduction in 30-day mortality.
These results, the researchers say, open the door to reevaluating how strictly SGLT2i need to be withheld before surgery. They also suggest that continued use of these medications in acute settings may be safer than previously thought.
Furthermore, the authors state that the data was observational in nature — the exact timing the patients took the medication was unknown. Additionally, the patient group comprised of white males over 60 years old, which makes it difficult to generalize the results to women and other age and ethnic groups.
For now, the findings are unlikely to change clinical practice overnight. But they highlight a growing recognition that blanket policies may need refinement as evidence evolves—and that individualized risk assessment could become the new gold standard in perioperative diabetes care.
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