Physical stress experienced by patients undergoing surgical procedures is well recognized to not only temporarily alter homeostasis, but also result in increased morbidity and mortality in patients requiring surgical intervention. New research published in April 2020 in JAMA Surgery explores the association between the presurgical use of the popular diabetic drug metformin and improved outcomes in patients with type 2 diabetes.
Lead author, Katherine M. Reitz, MD, from the University of Pittsburgh School of Medicine, and her team explored whether biguanide metformin, when used before surgery, was associated with a reduced risk of readmission and mortality. According to the authors, type 2 diabetes affects roughly 30% of Americans older than age 65 years, and half of those patients will likely need surgical intervention at some point during their lifetime. Also noted was the increased likelihood of impaired cardiovascular function in these diabetic patients undergoing major surgical procedures, with impaired inflammatory resolution leaving little physiologic reserve in these patients.
Using electronic health records, the researchers identified over 10,000 patients diagnosed with diabetes who underwent a major surgical procedure. Of these patients, 59% had taken metformin prior to surgery. The team hypothesized that the metformin patients would benefit from the drug’s anti-inflammatory properties. The analysis included 5,460 propensity score–matched patients with a mean age of 67.7 years, 2,866 (53%) of whom were women.
The team evaluated inflammation as evidenced by the neutrophil-to-leukocyte ratio and compared those values in patients who had and had not received preoperative prescriptions for metformin. The corresponding absolute risk reduction (ARR) and adjusted hazard ratio (HR) with 95% CI were calculated in the propensity score–matched cohort, with preoperative inflammation reduced in those with metformin prescriptions compared with those without them (mean neutrophil to leukocyte ratio, 4.5 [95% CI, 4.3-4.6] compared with 5.0 [95% CI, 4.8-5.3]; P <.001).
The team also examined readmission within 90 days of discharge, as well as all-cause postoperative mortality. Patients with reported presurgical metformin use had a reduced hazard for 90-day mortality (adjusted HR, 0.72 [95% CI, 0.55-0.95]; ARR, 1.28% [95% CI, 0.26-2.31]); and hazard of readmission, with mortality reported as a competing risk at both 30 and 90 days, (ARR, 2.09% [95% CI, 0.35-3.82] and ARR, 2.78% [95% CI, 0.62-4.95]), respectively.
The authors concluded, “The advantages are likely not disease specific, but instead the pleiotropic properties may modulate the stress response generated by a major surgical intervention or confer consistently good outcomes, regardless of the surgical procedure.” The authors added, “This study found an association between metformin prescriptions provided to individuals with type 2 diabetes before a major surgical procedure and reduced risk-adjusted mortality and readmission after the operation. This association warrants further investigation.”
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