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Original Investigation
April 8, 2020

Association Between Preoperative Metformin Exposure and Postoperative Outcomes in Adults With Type 2 Diabetes

Author Affiliations
  • 1Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • 2Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Pittsburgh, Pennsylvania
  • 3Clinical Analytics, UPMC Health Services Division, Pittsburgh, Pennsylvania
  • 4Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania
  • 5Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • 6Department of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • 7Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
  • 8Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • 9Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
JAMA Surg. Published online April 8, 2020. doi:10.1001/jamasurg.2020.0416
Key Points

Question  Are preoperative metformin prescriptions associated with a lower risk of postoperative mortality and readmission among patients with type 2 diabetes who underwent a major surgical intervention?

Findings  In this cohort study of 5460 patients with diabetes who had a major surgical procedure, preoperative prescriptions of metformin were associated with a statistically significant decrease in the risk of 90-day mortality as well as 30- and 90-day readmission compared with no such prescriptions.

Meaning  Findings from this study suggest that preoperative metformin prescriptions may be associated with decreased postoperative mortality and readmission compared with no preoperative exposure to this medication, but further research is needed to ascertain if this relationship is causal.

Abstract

Importance  Adults with comorbidity have less physiological reserve and an increased rate of postoperative mortality and readmission after the stress of a major surgical intervention.

Objective  To assess postoperative mortality and readmission among individuals with diabetes with or without preoperative prescriptions for metformin.

Design, Setting, and Participants  This cohort study obtained data from the electronic health record of a multicenter, single health care system in Pennsylvania. Included were adults with diabetes who underwent a major operation with hospital admission from January 1, 2010, to January 1, 2016, at 15 community and academic hospitals within the system. Individuals without a clinical indication for metformin therapy were excluded. Follow-up continued until December 18, 2018.

Exposures  Preoperative metformin exposure was defined as 1 or more prescriptions for metformin in the 180 days before the surgical procedure.

Main Outcomes and Measures  All-cause postoperative mortality, hospital readmission within 90 days of discharge, and preoperative inflammation measured by the neutrophil to leukocyte ratio were compared between those with and without preoperative prescriptions for metformin. The corresponding absolute risk reduction (ARR) and adjusted hazard ratio (HR) with 95% CI were calculated in a propensity score–matched cohort.

Results  Among the 10 088 individuals with diabetes who underwent a major surgical intervention, 5962 (59%) had preoperative metformin prescriptions. A total of 5460 patients were propensity score–matched, among whom the mean (SD) age was 67.7 (12.2) years, and 2866 (53%) were women. In the propensity score–matched cohort, preoperative metformin prescriptions were associated with 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 as a competing risk at both 30 days (ARR, 2.09% [95% CI, 0.35-3.82]; sub-HR, 0.84 [95% CI, 0.72-0.98]) and 90 days (ARR, 2.78% [95% CI, 0.62-4.95]; sub-HR, 0.86 [95% CI, 0.77-0.97]). Preoperative inflammation was reduced in those with metformin prescriptions compared with those without (mean neutrophil to leukocyte ratio, 4.5 [95% CI, 4.3-4.6] vs 5.0 [95% CI, 4.8-5.3]; P < .001). E-value analysis suggested robustness to unmeasured confounding.

Conclusions and Relevance  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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