A new trial suggests that dapagliflozin, an SGLT2 inhibitor, may significantly lower the risk of acute kidney injury following elective heart surgery, challenging existing peri-operative guidelines and opening new avenues for kidney protection.
Dapagliflozin, a diabetes drug in the SGLT2 inhibitor class, sharply cut the risk of acute kidney injury after elective cardiac surgery in a randomised trial published in JAMA, while causing very few cases of postoperative diabetic ketoacidosis. The findings are drawing attention because kidney injury remains one of the most common complications after heart surgery and has long lacked a proven preventive treatment. According to the study authors, the result suggests the problem may now be modifiable.
The MERCURI-2 trial enrolled 784 patients at seven hospitals in the Netherlands and gave half of them dapagliflozin, starting the day before surgery and continuing through the second day afterwards. Among the 778 patients who completed follow-up, the average age was 68, most were men, and the majority were White. The trial excluded people at especially high risk of ketoacidosis or with very advanced kidney disease, reflecting the safety concerns that have surrounded peri-operative use of SGLT2 inhibitors.
AKI developed in 28% of patients assigned to dapagliflozin, compared with 52% in the placebo group. Most cases were mild, but more severe kidney injury was also less common with the drug. The trial found no meaningful differences between the groups in length of hospital stay, intensive care stay, death, major cardiac or kidney events, or quality of life at 30 days. Atrial fibrillation and reoperation rates were also similar.
The low rate of ketoacidosis is likely to be the most important safety signal for clinicians. Only one patient in the dapagliflozin group developed the complication, despite long-standing guidance from groups including the American Diabetes Association and the UK Centre for Perioperative Care advising that SGLT2 inhibitors be stopped several days before surgery. The JAMA editorial accompanying the study argued that the balance of risk may deserve reconsideration, while also warning that the unusually high AKI rate in the placebo arm means the results should be interpreted carefully.
Abraham H. Hulst, the study’s co-author, told Medscape Medical News that the peri-operative period is not neutral for patients already taking these drugs, particularly those using them for heart failure or chronic kidney disease. He said the evidence was not yet enough to start dapagliflozin routinely before surgery outside a trial, but suggested there may be less reason to stop it in some patients than previously thought. Other experts, including Elif Ekinci of the University of Melbourne, said the findings were consistent with emerging observational data and could point to a new approach to kidney protection if confirmed in larger studies.
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