From the Journals

Metformin use linked to improved surgery outcomes



Patients with type 2 diabetes who take metformin may have lower risk-adjusted mortality and readmission rates after surgery than do those who don’t take metformin, findings from a large retrospective cohort study suggest.

Of 10,088 individuals with diabetes who underwent a major surgery requiring hospital admission between January 1, 2010, and January 1, 2016, a total of 5,962 (59%) had received a prescription for metformin in the 180 days before surgery, and 5,460 of those patients were propensity score–matched to controls who did not receive a metformin prescription.

The study participants had a mean age of 67.7 years and underwent surgery requiring general anesthesia and postoperative admission at any of 15 hospitals in a single Pennsylvania health system. In addition to being prescribed metformin within 180 days before surgery, they also had metformin on their list of active medications at their most recent preoperative encounter before the surgery. The were followed until December 18, 2018.

In all, the 90-day and 5-year mortality hazards were reduced by 28% and 26%, respectively, in the metformin prescription recipients, compared with the propensity score–matched controls (hazard ratios, 0.72 and 0.74, respectively), Katherine M. Reitz, MD, and colleagues at the University of Pittsburgh reported in JAMA Surgery.

The readmission hazard – with mortality as a competing risk – was reduced by 16% at 30 days and 14% at 90 days (sub-HRs, 0.84 and 0.86, respectively), the researchers found.

“Hospital readmissions among those with preoperative metformin prescriptions were observed by postdischarge days 30 and 90 (304 [11%] and 538 [20.1%], respectively), whereas among those without prescriptions, 361 readmissions (13%) occurred by day 30 and 614 (23%) by day 90,” they wrote.

The investigators also noted that inflammation was reduced in patients who received a metformin prescription, compared with those who did not (mean preoperative neutrophil to leukocyte ratio, 4.5 vs. 5.0, respectively).

“In the full cohort, multivariable regression analysis similarly demonstrated that metformin was associated with a reduced hazard for both 90-day and 5-year mortality (adjusted HRs, 0.77 and 0.80, respectively) and for 30-day and 90-day readmission (aHR, 0.83 and 0.86), with mortality as a competing risk,” they added.

The findings support those from previous studies showing a decrease in all-cause mortality among diabetes patients taking metformin, said the researchers, noting that those patients had fewer age-related chronic diseases.

“These associations may reflect the anti-aging properties of metformin against the onset of disease or diabetes-associated complications. This study extends these finding by demonstrating that preoperative metformin prescriptions were associated with a reduction in postoperative mortality and readmission, a surrogate for postoperative complications, and with long-term mortality,” they wrote.

The study was limited by a number of factors, such as the potential for residual confounding inherent in retrospective analyses and a lack of adequate power to evaluate the association between metformin use and outcomes for individual surgical procedures. But the authors added that the findings are of note, because adults with comorbidities, such as diabetes, have less physiological reserve and an increased postoperative mortality and readmission rate. The results, therefore, warrant investigation with a prospective randomized clinical trial, they concluded.

In an accompanying editorial, Elizabeth L. George, MD, and Sherry M. Wren, MD, of Stanford (Calif.) University wrote that the study “demonstrates how variables, besides coexisting medical diseases, can affect surgical outcomes.”

“Metformin now joins beta-blockers, statins, and immunonutrition as preoperative agents associated with improved surgical outcomes,” they wrote, adding that future studies should factor in statin use and whether those and other medications should be continued postoperatively because metformin is often held after surgery owing to concerns about contrast agent interactions, whereas statin continuation is recommended.

Future studies of metformin in this setting should exclude patients who are taking statins, or look at possible interactions between the two agents, they said, adding that they would be “interested in seeing a subanalysis of this data set that excludes patients who were prescribed statins.”

“Those data would further solidify the role of metformin as a possible modifiable perioperative factor,” they wrote.

The study was funded by the University of Pittsburgh Medical Center and by grants from the National Heart, Lung, and Blood Institute and the National Institutes of Health. Dr. Reitz reported having no disclosures. Dr. George and Dr. Wren also reported having no disclosures.

SOURCE: Reitz K et al. JAMA Surg. 2020 Apr 8. doi: 10.1001/jamasurg.2020.0416.

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