April 24, 2020
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Preoperative metformin reduces mortality, readmission risks for patients with type 2 diabetes

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Katherine Reitz
Katherine Reitz

Patients with type 2 diabetes who were prescribed metformin prior to a major surgery had reduced risks for mortality and readmission in the 90 days following the procedure, according to a retrospective cohort study published in JAMA Surgery.

“Exposure to metformin appears to protect our bodies against a lifetime of small stressors, both delaying the onset of diseases associated with aging, including cancer and cardiovascular disease, as well as potentially increasing our overall life expectancy,” Katherine M. Reitz, MD, a general surgery resident in the department of surgery and a T32 postdoctoral scholar in the Clinical Research, Investigation and Systems Modeling of Acute Illness Center at the University of Pittsburgh School of Medicine, told Healio. “In our study, patients exposed to metformin demonstrated a reduction in both hospital readmission, representing surgical complications, as well as death following a major surgical intervention. Therefore, our work extends the potential protective effects of metformin to not just the cumulative small stressors experienced throughout a lifetime of aging, but also the major stress of a surgical intervention.”

Mortality, complications risks lowered

Reitz and colleagues analyzed data from electronic health records from January 2010 to January 2016 on 2,730 adults with type 2 diabetes who had preoperative metformin prescriptions in the 180 days prior to undergoing a major surgery and 2,730 propensity-matched without metformin exposure (mean age, 67.7 years; 53% women; 89% white; mean BMI, 33.5 kg/m2; 33% treated with insulin; mean HbA1c, 7.1%). The primary outcome was all-cause mortality within 90 days of discharge; secondary outcomes were 30-day mortality, 30-day and 90-day readmission, 5-year survival and preoperative inflammation determined by mean neutrophil to leukocyte ratio. Median follow-up was more than 4.5 years for both groups. Among those in the preoperative metformin group, 95% continued the agent during the year following surgery; among the no-metformin group, 8% had evidence of starting the agent after surgery.

Patients with type 2 diabetes who were prescribed metformin prior to a major surgery had reduced risks for mortality and readmission in the 90 days following the procedure.
Source: Adobe Stock

Among the metformin group 49 (2%) patients died within 30 days of discharge, 89 (3%) within 90 days and 360 (13%) within 5 years. Among the no-metformin group, 56 (2%) patients died within 30 days of discharge, 124 (5%) within 90 days and 471 (17%) within 5 years. Mortality risks were more than 25% lower for the metformin vs. no-metformin group at 90 days (adjusted HR = 0.72 [95% CI, 0.55-0.95]; absolute risk reduction = 1.28% [95% CI, 0.26-2.31]) and at 5 years (HR = 0.74; 95% CI, 0.65-0.85).

Among the metformin group, 304 (11%) were readmitted within 30 days of discharge and 538 (20%) within 90 days vs. 361 (13%) and 614 (23%), respectively, among the no-metformin group with reduce readmission risks for the metformin group (30 days, ARR = 2.09% [95% CI, 0.35-3.82]; 90 days, ARR = 2.78% [95% CI, 0.62-4.95]).

Preoperative inflammation was lower among those with vs. without metformin (mean NLR, 4.5 vs. 5.0; P < .001).

“Just as an athlete would train for a major event, providers should be helping patients prepare for surgery to yield the best possible outcomes,” Reitz said. “This preparation should include a healthy lifestyle and optimizing all medical conditions, including blood sugar control among patients with type 2 diabetes. Beyond this, the anti-inflammatory and anti-aging properties of metformin may confer improved postoperative outcomes in all patients vulnerable to the stress of surgery.”

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Ongoing inquiry

The study results were the impetus for initiating further trials of presurgical therapies, Reitz said.

Metformin is the first of many future placebo-controlled trials evaluating perioperative effectiveness of therapies hypothesized to improve postoperative outcomes in high-risk, older adults undergoing a major surgical intervention,” Reitz said. “The results of this actively enrolling trial, Strategies to Promote ResiliencY (SPRY) will better guide the use of pharmacologic prehabilitation and potential indications for delaying the operative date in order to better prepare and train our patients for surgery.”

In an accompanying editorial, Elizabeth L. George, MD, and Sherry M. Wren, MD, from the department of surgery at Stanford University School of Medicine, wrote that the study demonstrated that other variables besides comorbidities can affect a patient’s surgical outcome.

“Metformin now joins beta 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,” George and Wren wrote.

“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. … These data would further solidify the role of metformin as a possible modifiable preoperative factor,” they wrote. – by Erin T. Welsh

Disclosures: Reitz, George and Wren report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.