In patients undergoing elective cardiac surgery, four doses of dapagliflozin beginning the day before the operation significantly reduced the incidence of postoperative acute kidney injury during the 7-day recovery period, according to a multicenter placebo-controlled trial published in JAMA. The trial found that dapagliflozin lowered AKI incidence to 28% compared with 52% in the placebo group, though editorialists noted the trial lacked the statistical power to definitively show clinical benefits for severe stage 3 AKI or major adverse cardiovascular events.
MERCURI-2 Trial Results and Renal Protection Data
The randomized, double-blind MERCURI-2 trial tracked 784 adult participants across seven hospitals in the Netherlands between 2023 and 2025. According to Abraham Hulst, MD, PhD, of Amsterdam University Medical Center, and his research colleagues, patients received either a daily 10-mg oral dose of dapagliflozin (Farxiga) or a placebo beginning the day before surgery and continuing through the second postoperative day.
The short course of SGLT2 inhibitor therapy yielded a relative risk of 0.54 (95% CI 0.45-0.65) for acute kidney injury within 7 days. After multivariable adjustment, the odds ratio stood at 0.36 (95% CI 0.27-0.48). Study follow-up was completed by 99% of the trial cohort, with 88% of the dapagliflozin arm and 87% of the placebo group taking all four assigned tablets.
Did you know? Cardiac surgery-associated AKI occurs in roughly 10% to 40% of cases. Approximately 11% of affected patients develop acute kidney disease, and 6% progress to chronic kidney disease within a year, according to background data cited by the trial investigators.
Clinical Implications and Editorial Caution
Despite the strong primary findings, JAMA editor Wolfgang Winkelmayer, MD, MPH, ScD, of Baylor College of Medicine in Houston, and Glenn Chertow, MD, MPH, of Stanford School of Medicine in California, pointed out that the magnitude of the primary treatment effect invites some skepticism regarding biological plausibility. In an accompanying editorial, the duo urged that future investigations into AKI prevention require larger sample sizes.
“Nevertheless, given the magnitude of the observed benefit, the likelihood that the provision of an SGLT2 inhibitor in this setting provides no benefit or results in harm is extremely low,” Winkelmayer and Chertow wrote.
The editorialists also highlighted a notable irony regarding clinical guidelines. The American Diabetes Association, the U.K. Centre for Perioperative Care, and the U.S. Food and Drug Administration have previously recommended withholding SGLT2 inhibitors for 3 days before surgery to mitigate the risk of euglycemic diabetic ketoacidosis. However, Winkelmayer and Chertow reasoned that this very low risk does not outweigh the potential prevention of postoperative AKI.
Safety Profiles and Study Limitations
The trial tracked adverse events closely across both cohorts. Atrial fibrillation occurred in 45% of patients in both the dapagliflozin and placebo groups. Reoperation rates were comparable as well, observed in 11% of the dapagliflozin arm versus 10% in the placebo group.
Hulst and colleagues noted that urine output definitions heavily influenced the high AKI incidence recorded in the control group. Among participants meeting the primary outcome, 48% in the placebo group and 21% in the dapagliflozin arm triggered the criteria based strictly on reduced urine output rather than creatinine spikes.
Furthermore, the researchers acknowledged that the study population possessed limited generalizability, consisting predominantly of white men with a median age of 68 years and an estimated glomerular filtration rate of 80 mL/min/1.73 m2. About one in ten participants had diabetes.
Frequently Asked Questions
What is dapagliflozin?
Dapagliflozin, marketed as Farxiga, is an SGLT2 inhibitor currently approved to protect kidney and heart health in adults with chronic kidney disease at risk of progression, reduce heart failure hospitalizations, and provide glycemic control in type 2 diabetes.
How was acute kidney injury defined in the MERCURI-2 trial?
AKI was defined using Kidney Disease: Improving Global Outcomes criteria: an increase in serum creatinine by at least 0.3 mg/dL within 48 hours, a 1.5-fold creatinine increase within 7 days, or urine output below 0.5 mL/kg/h for 6 to 12 hours.
Did the trial evaluate long-term cardiovascular outcomes?
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