medwireNews: Sodium-glucose cotransporter (SGLT)2 inhibitor use is associated with a small but significantly increased risk for postoperative euglycemic ketoacidosis (eKA) but lower risks for postoperative acute kidney injury (AKI) and mortality, US study findings indicate.
Writing in JAMA Surgery, Matthieu Legrand (University of California, San Francisco) and co-authors explain that an increasing number of case reports and small retrospective studies have suggested that the risks for postoperative eKA and AKI are elevated among patients using SGLT2 inhibitors prior to surgery.
“However, case reports and case series are prone to admission, selection, and reporting bias,” they remark. “Therefore, the actual risks of eKA and postoperative acute kidney injury and death among SGLT2 [inhibitor] users is unknown.”
To address this, Legrand et al compared surgical outcomes between people within the Veterans Affairs Health Care System who had a history of long-term SGLT2 inhibitor use (three or more outpatient prescriptions within 3 months prior to surgery or less than a 180-day gap since the most recent fill) and a propensity score matched control group of people who were not using SGLT2 inhibitors.
Empagliflozin was the most used SGLT2 inhibitor (99.7%) and there was a progressive increase in the proportion of patients using SGLT2 inhibitors who underwent surgery; 80% of the patients underwent surgery between 2020 and 2022, the researchers note.
They report that the 7439 long-term, preoperative SGLT2 inhibitor users (97% men, mean age 68 years) who underwent inpatient surgical procedures between 2014 and 2022, had a significant 11% higher risk for eKA within 7 days of surgery than the 33,489 controls who were matched by demographics, comorbidity, and surgical characteristics.
Specifically, the eKA incidence was 29.7% among SGLT2 inhibitor users and 27.6% among nonusers. Patients who developed eKA had a median hospital length of stay of 6 days compared with 3 days for those without eKA.
The researchers suggest that the increased risk for eKA may partly be explained by “the reduction in oral carbohydrate intake during [the perioperative period] and the effect of surgical stress, which can increase insulin requirements and metabolic demand..
Conversely, Legrand and team observed that SLGT2 inhibitor users had a significant 31% lower risk for developing AKI within 30 days of surgery than nonusers, and a significant 30% lower risk for 30-day mortality.
Postoperative AKI incidence was 5.1% in the SGLT2 inhibitor group versus 7.1% in the control group, while 30-day mortality rates were 1.1% and 1.6%, respectively.
A subgroup analysis of patients undergoing cardiac surgery, which the researchers say is often associated with intense stress, a pronounced metabolic response, and prolonged procedure duration, showed that the incidence of eKA was a significant 30% higher with versus without SGLT2 inhibitor use, at 56.4% versus 49.8%. The were no significant differences between these two subgroups in the risks for AKI or postoperative mortality.
The investigators comment that the US FDA recommends suspension of SGLT2 inhibitors for 72 to 108 hours before elective surgery to lower the risk for postoperative eKA but the exact timing of the last administration was unknown in the current analysis. This meant they were unable to determine the clinical impact of withholding SGLT2 inhibitors prior to surgery.
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