Metformin May Protect Diabetes Patients from Surgical Complications

A new study shows promising results

With Sherry Wren MD and Brett Guinto DO

Metformin shows promising anti-inflammatory effects in a new study.

When any patient has surgery, physicians worry about the stress a procedure can put on a body. For patients with type 2 diabetes – half of whom are expected to undergo surgery in their lifetime, surgical stresses may be even more dangerous. These stressors are potentially added to comorbidities such as kidney dysfunction or general ill-health experienced by older patients with type 2 diabetes. But there may be a way to ameliorate those risks: metformin, the most commonly prescribed drug for those with type 2 diabetes, has anti-inflammatory properties that might protect patients from potential complications.

Metformin’s protective effects in surgical patients with type 2 diabetes

A new study published in JAMA Surgery looked at the possibility of metformin’s protective effects in surgical patients with type 2 diabetes, and several key data points give hope that it could potentially limit risks among that patient group. The retrospective cohort study looked at patients with type 2 diabetes who had at least one presurgical prescription of metformin in the 180 days prior to their surgery. They were matched with like patients who did not receive that medication. Study participants came from 15 academic medical centers in a single Pennsylvania healthcare system. The authors found records of just under 6000 patients in the group that took metformin, and 4200 for the group that did not. The records came from patients who had surgery over a six year period ending January 1, 2016. In both groups, more than 90% of the surgeries were elective, with just 7% and 9% respectively being for emergencies.

The primary outcome was 90 day postoperative mortality rates. Authors chose secondary outcomes of 30 day mortality rates, 5 year survival rates, 30 and 90 day readmission rates, and neutrophil to leukocyte ratio (NLR), a general marker of inflammation. 

Among the group who took metformin prior to surgery, mortality rates were 2% by day 30 post surgery, 3% at day 90, and 13% at the five year mark. In those who did not take the drug, the outcomes were 2% mortality at day 30, 5% at day 90, and 17% by five years.

Readmission rates for the group who had the prescription were 11% after 30 days and 20% after 90 days, compared to 13% and 23% among those who did not take metformin. Prior to surgery, patients on metformin had lower mean preoperative NLR compared to those without.

Metformin is associated with a reduction in all-cause mortality

This is not the first study to find a relationship between metformin use and a reduction of all-cause mortality. However, there are several limitations to this study, the authors noted, including that there were different surgical approaches used – laproscopic versus traditional; different types of surgeries – vascular, cardiothoracic, neurological, orthopedic, or general; the advanced age and comorbidity status of the study group; and that this was a retrospective rather than prospective study.

Perhaps most limiting, according to one of the authors of the accompanying editorial letter, Sherry M. Wren, MD of the department of surgery at Stanford University, is that authors did not control for whether patients were also on statins – a class of drug known to offer protective effects to many surgical patients. It is considered both an anti-inflammatory and an immune-modulating agent. “More than 60% of the patients in the study – both in the metformin group and in the control group, were on statins, so if they control for that, would there still have been a positive effect?” she asks.

Wren acknowledges that there is ample evidence that metformin has “other effects that are not related to what it is prescribed for.” She points to a study that is currently underway looking at metformin use in vascular surgery and whether it can prevent abdominal aortic aneurysms. “It’s not surprising that metformin has other effects, but I need to see more about this.”

Ideally, Wren says she would like to see a prospective clinical trial looking at metformin use in surgical patients that controls for statin use. “Statins are phenomenally cheap and well-tolerated,” she says. “Do we know that people without diabetes can take metformin and not have issues? Maybe.”

However, she wonders whether there is appetite among those who fund such work to do this kind of study – it would be expensive, and in the United States, “there seems to be an aversion to randomized clinical trials.”

In the absence of a clinical trial, at the very least Wren would like to see the authors reanalyze the data controlling for statin use. As it stands, these findings, while interesting, are not enough for her to change her surgical practices.

Patients being cared for in a hospital setting are usually taken off metformin, Wren says. That class of drug can create issues with contrast studies. “I have never continued a patient’s metformin in the hospital, so that’s another angle to look at – if it is not continued in the hospital, are there still changes that happen in outcomes? But for my practice to change, I need to see more analysis. Diabetes itself is a risk factor in surgery, but how much is difficult to sort out. If this can indeed improve outcomes as this study suggests, that would be great. But until I see some more analysis of this data, I’m not going to get too excited.”

Brett Guinto DO, FACP, FACE, who works with the Woodland Hills Medical Center endocrinology and metabolism service, notes that there is “potential promise for those diabetes patients on metformin who undergo major surgery,” but for now he will view it solely as a first line oral therapy for appropriate patients with insulin resistance.

“With the advent of big data analytics, we can look at outcomes in a bigger way, and in a different way,” Wren concludes. “You can have really large data sets that might give you insight into the protective mechanisms of different drugs on outcomes. The hard thing becomes when they take these drugs and put them into clinical trial. Then you have to determine if can you see the same outcome.”

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