New Study Indicates Preoperative Metformin May Improve Post-Operative Outcomes in Major Surgery

^{By: Yvette C. Terrie, RPh, Consultant Pharmacist}

Research has demonstrated that adults with comorbidities have less physiological reserve and an augmented rate of postoperative mortality and readmission after the stress of a major surgical intervention. According to a recent study published in JAMA Surgery, the use of preoperative metformin may be linked with diminished postoperative mortality and readmission among patients with type 2 diabetes undergoing a major surgical procedure.

In this cohort study, Katherine Reitz, MD, of the University of Pittsburgh School of Medicine, and colleagues evaluated postoperative mortality and readmission among individuals with diabetes with or without preoperative prescriptions for metformin. In this cohort study, data was obtained from the electronic health record of a multicenter, single health care system in Pennsylvania. The data included 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. The researchers utilized 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.

 The results of the study revealed that:

• Among the 10,088 individuals with diabetes who underwent a major surgical intervention, 5,962 (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 < 0.001). E-value analysis suggested robustness to unmeasured confounding.
• The study also found lower risk of 5-year mortality with metformin taken before surgery (HR 0.74, 95% CI 0.65-0.85, P < 0.001).

The study results demonstrate that preoperative metformin use was associated with lower adjusted hazard ratios of postoperative mortality and readmission. This study also demonstrates how variables besides coexisting medical diseases can affect surgical outcomes. The researchers concluded that the results of 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 merits further investigation.

In an accompanying commentary the authors of the study noted. “Metformin now joins β-blockers, statins, and immunonutrition as preoperative agents associated with improved surgical outcomes. It may be only a matter of time before optimization of postoperative outcomes with perioperative medications and supplements becomes a standard. To answer this question more completely, further analysis or future trials should factor in statin use, as well as whether medications are continued in the postoperative period.”

Yvette C. Terrie, R.Ph., Consultant Pharmacist, Medical Writer and creator of A Pharmacist’s Perspective (https://apharmacistsperspective.blogspot.com ).

References

1. Reitz KM, Marroquin OC, Zenati MS, et al. Association Between Preoperative Metformin Exposure and Postoperative Outcomes in Adults With Type 2 Diabetes. JAMA Surg. Published online April 08, 2020. doi:10.1001/jamasurg.2020.0416
2. Monaco K. Metformin Appears to Shield Diabetic Patients From Post-Op Death. Medical Page Today website. https://www.medpagetoday.com/primarycare/diabetes/85887 . Published April 21, 2020. Accessed April 21, 2020.
3. Busko M. Could Preoperative Metformin Improve Major-Surgery Outcomes? Medscape website. https://www.medscape.com/viewarticle/928879 . Published April 17, 2020. Accessed April 21, 2020.
4. George EL, Wren SM. Improving Outcomes After Surgery—An Old Medication With Unexpected Benefits. JAMA Surg. Published online April 08, 2020. doi:10.1001/jamasurg.2020.0417