Improved Post-Surgical Outcomes in Patients Using Metformin 

Feb 13, 2021 Editor: Steve Freed, R.PH., CDE
Author: Abdullah Al-Ajmi, PharmD Candidate, Skaggs School of Pharmacy and Pharmaceutical Sciences

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Metformin use was associated with lower inflammatory markers before surgery, leading to improved outcomes post-surgery. 

Around a third of patients >65 years in the U.S. have type 2 diabetes (T2DM). Due to diabetes complications, renal and cardiac comorbidities are common in many patients, leading to impaired inflammatory responses and reduced time to recovery. Also, around half of this patient population undergoes surgical treatment during their lifetime. Therefore, these effects may lead to increased morbidity and mortality post-surgery.

Patients with T2DM have commonly been prescribed metformin as first-line therapy. In addition to its impact on blood glucose control, it has been shown to reduce chronic inflammation. These effects have been studied in diseases linked with the aging process, such as cardiovascular and renal diseases. Previous literature regarding the use of metformin has shown that it reduces all-cause mortality and cardiovascular and renal complications. However, whether metformin use pre-surgery can improve patients’ outcomes post-surgery was not studied before.  

A new study aimed to assess the effect of metformin on post-surgical outcomes in patients with T2DM. The study design was retrospective, including patients with T2DM who underwent surgery and were eligible for metformin use. It excluded patients with type 1 diabetes or impaired renal function, since metformin is not indicated in those cases. The investigators compared the patients’ outcomes based on whether they received metformin before surgery or not. Since metformin’s effect on inflammation is based on its use over time, patients’ glycemic control was not considered in the enrollment process. They included patients with an increased risk of mortality or readmission.  

The study data was collected from January 2010 to January 2016, and the follow-up continued to December 2018. 

Metformin exposure was considered if the patient received at least one prescription within six months before surgery and prescribed the last doctor’s prescription before surgery. Patients who did not meet these criteria were considered not exposed to metformin and fell in the comparison group. Those who are not indicated to use metformin were excluded from the study. The study identified the primary outcome to be 90 days mortality post-surgery. Additionally, secondary outcomes were identified, including 30-day mortality, readmission within three months post-surgery, 5-year survival rate, and the level of the inflammatory marker neutrophil to leukocyte ratio (NLR) pre-surgery. 

The study included 5,460 patients who were matched at a 1:1 ratio between the study groups. Patient characteristics were similar between the groups. In the metformin group, around 2% of deaths were reported within a month of surgery. Also, 3% of deaths were reported after three months and 13% in the 5th year. On the other hand, the non-metformin group showed a similar 2% death rate in the first month, but the rates increased to 5% and 17% by three months and five years, respectively. The risk reduction associated with metformin use is considered statistically significant (1.28%; 95% CI, 0.26–2.31). The results also indicate that metformin use was associated with a statically significant reduction in 90-day and 5-year mortality. These outcomes were similar to most surgical interventions except in neurosurgery, which did not show a significant risk reduction with the use of metformin. When comparing hospital readmissions, metformin use was associated with significantly lower readmission rates from 1 to 3 months after discharge than patients who did not receive metformin. Moreover, patients in the metformin group had lower NLR levels before surgery.  

The study findings suggest that metformin has additional mechanisms of action to its known means for glycemic control. The reduction of the NLR before surgery is associated with a decrease in morbidity and mortality post-surgery. The study has several limitations, one of which the possibility of confounding variables due to its design. One reason is that the type of surgery was evenly distributed between cohorts. Different surgeries can cause additional surgical stress to the patients, which may affect the study’s outcome. Also, the retrospective nature may introduce selection bias during the data collection phase. Furthermore, the author indicated that the mortality and admission rate might have been misrepresented.  

Practice Pearls: 

• Metformin use in patients with T2DM is associated with a reduced mortality risk post-surgery. 
• Readmission post-discharge is reduced with metformin use before surgery in patients with T2DM. 
• Patients with T2DM on metformin have lower inflammatory markers before surgery, leading to improved outcomes post-surgery. 

Reitz, Katherine M. et al. “Association Between Preoperative Metformin Exposure And Postoperative Outcomes In Adults With Type 2 Diabetes”. JAMA Surgery, vol 155, no. 6, 2020, p. e200416. American Medical Association (AMA), doi:10.1001/jamasurg.2020.0416.  

Campbell, Jared M. et al. “Metformin Reduces All-Cause Mortality And Diseases Of Ageing Independent Of Its Effect On Diabetes Control: A Systematic Review And Meta-Analysis.” Ageing Research Reviews, vol 40, 2017, pp. 31-44. Elsevier BV, doi:10.1016/j.arr.2017.08.003.  

Abdullah Al-Ajmi, PharmD Candidate, Skaggs School of Pharmacy and Pharmaceutical Sciences