Abstract
Background: Metformin is an oral antidiabetic agent belonging to the biguanide class of antidiabetics. Possible novel applications for metformin in cardiovascular disease might exist. The aim of this study was to verify a possible association between pre-operative metformin administration and protection against ischemia-induced liver injury in diabetic patients undergoing coronary artery bypass grafting (CABG) surgery.
Methods: A retrospective case-control series was conducted at a single center. Two hundred consecutive diabetic patients underwent isolated on-pump CABG during a 12-month span (July 2015 - July 2016). Metformin was uninterrupted in patients who took this drug prior to CABG; 68 patients were metformin users (34%) while 132 patients were taking other antidiabetic agents (66%). Liver enzymes and other organ markers were consecutively recorded daily for 7 days after surgery and expressed as medians with interquartile range (IQR).
Results: Both the metformin and non-metformin group of patients had similar pre-operative demographic characteristics. The median (IQR) post-operative cardiac enzyme creatinine kinase (CK) MB fraction was significantly lower in the metformin group [46.4 U/L (35.8-66.5) vs. 66.5 U/L (44-94.5), P=0.005]. Total bilirubin [0.58 (0.48-0.82) mg/dL vs. 0.67 (0.56-0.95) mg/dL, P=0.021], the transaminase aspartate aminotransferase (AST) [32.5 U/L (25.0-42.0) vs. 37.5 U/L (28.5-56), P=0.011], the transaminases alanine aminotransferase (ALT) [48.5 U/L (40.0-64.0) vs. 57.0 U/L (44.0-77.0), P=0.040] and lactate dehydrogenase (LDH) [320.0 U/L (273.5-367.2) vs. 356.5 U/L (289.5-427), P=0.014] were significantly lower in the metformin group. No differences were noted in clinical outcomes.
Conclusions: In this limited retrospective study, the diabetic patients who took metformin before and after undergoing CABG appeared to have a reduced post-operative surge in the total bilirubin and transaminase liver enzymes. Metformin's role in mitigating oxidative stress in liver cells might explain this observation. Further experimental studies are warranted to verify this possible effect.