Via Research Recognition Day 2024 VCOM-Carolinas

Educational Reports

Assessing whether metformin usage on type II diabetic patients vaccinated and unvaccinated for COVID-19 has a positive benefit towards patient survival and the correlation between ventilator usage and morbidities Vineet Madishetty, OMS-IV, Mark Dawod, MS, OMS-III, Lynn Campbell, D.O., FACOEP, FACEP Edward Via College of Osteopathic Medicine - Carolinas Campus, Spartanburg, SC

Discussion & Conclusion

Introduction

Results

References ● Arnett, S. (2021, March 10). What we know about COVID-19 and the inflammatory response. Drug Target Review. Retrieved March 8, 2022, from https://www.drugtargetreview.com/article/85765/what-we-know-about-covid-19-and-the inflammatory-response/ ● Bailey, C. J. (2017). Metformin: historical overview. Diabetologia, 60(9), 1566 – 1576. https://doi.org/10.1007/s00125 017-4318-z ● Bailey, C. J., & Gwilt, M. (2022). Diabetes, Metformin and the Clinical Course of Covid-19: Outcomes, Mechanisms and Suggestions on the Therapeutic Use of Metformin. Frontiers in pharmacology, 13, 784459. https://doi.org/10.3389/fphar.2022.784459 ● Chan, L. E., Casiraghi, E., Laraway, B., Coleman, B., Blau, H., Zaman, A., Harris, N., Wilkins, K., Gargano, M., Valentini, G., Sahner, D., Haendel, M., Robinson, P. N., Bramante, C., & Reese, J. (2022). Metformin is Associated with Reduced COVID-19 Severity in Patients with Prediabetes. medRxiv : the preprint server for health sciences, 2022.08.29.22279355. ● Usman, A., Bliden, K. P., Cho, A., Walia, N., Jerjian, C., Singh, A., Kundan, P., Duhan, S., Tantry, U. S., & Gurbel, P. A. (2022). Metformin use in patients hospitalized with COVID-19: lower inflammation, oxidative stress, and thrombotic risk markers and better clinical outcomes. Journal of thrombosis and thrombolysis, 53(2), 363 – 371. https://doi.org/10.1007/s11239-022-02631-7 Additional variables could be assessed in future studies to rule out this potential factor. Lastly, the data analyzed was specific to hospitals within the Spartanburg Regional Healthcare System. Expanding the study to larger regions and hospital systems including those in other states has potential to strengthen the data. ● We would like to thank Angela Wilson, PhD Biostatistician, Dorothy Williams, Data Quality Manager and Miles Lane, Senior Systems Analyst at SRMC for collecting, and de-identifying information from patient charts for our research ● We would also like to thank Dr. Alexis Stoner, PhD, MPH for guiding us during the beginning stages of the project SRHS IRB committee approval received on March 20th, 2023, Protocol #: 2022573-1 Acknowledgements Patient mortality rate in the study population was found to be statistically significantly higher in patients not currently receiving metformin for their T2DM. Ventilator requirement rate was also found to be elevated in those not on Metformin. Meanwhile, the average length of stay was deemed higher in the population receiving metformin therapy. It is likely possible that the there were other factors contributing to the average length of stay being longer despite being on metformin therapy. These results supports that metformin lessens the likelihood of serious adverse outcomes in T2DM patients with COVID-19. Pneumonia, PE, and DVT rates were all found to be increased in the subset of patients not receiving metformin therapy for their TD2M, although these results were not statistically significant within a 95% confidence interval. When vaccination status was analyzed for those T2DM patients on metformin and vaccinated for COVID, they were found to have a lower complication rate, mortality rate, and ventilator use rate compared to their non-vaccinated counterparts. The results showed that type 2 diabetics who were on metformin therapy did in fact see better clinical outcomes when compared to their counterparts, thus showing a positive relationship between metformin usage and the overall health of patients affected with COVID-19. This study focused on the effects of metformin specifically in patients with T2DM. Future studies should be conducted to assess the effects other diabetic medications with alternative mechanism of actions such as sulfonylureas, GLP-1 receptor agonists, SGLT-2 inhibitors, and DPP-4 inhibitors. Additional studies should be conducted to assess metformin's effects with other viruses. Metformin is the mainstay first line treatment for T2DM, and patients not currently on metformin therapy may have additional comorbidities or may not be receiving medical treatment altogether.

Metformin was first discovered in 1922 and was initially introduced as a treatment option for influenza. Later discoveries revealed the biguanides effectiveness in combating Type 2 diabetes mellitus (T2DM) by: decreasing hepatic glucose production through gluconeogenesis, decreasing glucose intestinal absorption, and increasing pancreatic insulin sensitivity, decreasing overall serum glucose levels. Due to this unique drug mechanism, the project intended to study how metformin may alleviate some of the challenges faced regarding COVID-19, a virus that continues to be a significant obstacle in the medical community. Objectives: ● Primary: Determine if patients who have a history of T2DM that are on metformin have better clinical outcomes when diagnosed with COVID-19 then those not on the medication. ● Secondary: Assess use of metformin on T2DM in regard to length of hospital stays, duration of ventilator usage, and the necessity for physical rehabilitation after recovery from COVID-19. Hypotheses: ● Metformin will have a difference in lessening the likelihood of serious adverse outcomes such as mortality, ventilator use, ECMO use, and length of hospital stay. ● Patients with TDM2 taking metformin and having received a COVID-19 vaccination prior to hospital presentation will have a lower likelihood of serious adverse outcomes. ● TDM2 patients taking metformin and admitted to the hospital with COVID-19 will have a lower morbidity. ● Retrospective chart review was conducted of patients diagnosed with COVID-19 and T2DM seen in the Spartanburg Regional Healthcare System ● Study range was between March 24th 2020 and March 25th 2022. ◆ 386 patients were on Metformin therapy ◆ 3,010 patients were not on Metformin therapy ● March 26th, 2021 became the first available date for patients aged 16 and older to be eligible for COVID-19 vaccination (DHEC, 2021). ◆ Patients were then separated based on metformin and COVID-19 vaccination status on admission ◆ 3,360 unvaccinated patients. ◆ 36 patients who were vaccinated prior to the encounter ● Comorbidities that were analyzed included: ◆ Acute myocardial infarction (AMI), Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, Deep Vein Thrombosis (DVT), Pulmonary Emboli (PE), and the requirement of ventilation assistance machines and average length of requirement. ● The patient’s average length of stay (ALOS) and subsequent admissions within the ● Statistical analysis was conducted with a 95% confidence level. Univariate analysis was conducted using a 2-tailed two- sample student’s t -tests and Wilcoxon rank-sum tests to compare means or medians. Pearson’s chi -squared test were conducted for comparison of categorical variables. Methods 30 days following discharge were additionally investigated. ● Exclusion criteria included: patients less than 18 years of age.

Figure 1: Complication rates in T2DM patients on Metformin therapy vs. Not on Metformin therapy. “Had complications” group includes patients with AMI, asthma, CHF, COPD, DVT, Mortality, PE, Pneumonia, or ventilation requirement

Figure 2: ALOS in T2DM patients on Metformin therapy vs. Not on Metformin therapy

Metformin Group No Metformin Had Metformin

Encounters Patients ALOS Complication Rate Mortality Rate Ventilator Use Rate

3,010

2,597 8.03 365 10.95 2,882 8.36

53.85% 51.04% 53.53%

9.00% 3.37% 8.36%

9.07% 7.25% 8.86%

386

Total

3,396

Vaccine Group

Encounters Patients ALOS Complication Rate Mortality Rate Ventilator Use Rate

No Vaccine Recorded

3,360

2,848 8.38

53.66% 41.67% 53.53%

8.45% 0.00% 8.36%

8.87% 8.33% 8.86%

COVID Vaccine Before Encounter

36

35 6.89

Total

3,396

2,882 8.36

Metformin Group No Metformin

Encounters Patients ALOS Complication Rate Mortality Rate Ventilator Use Rate

3,010 1,128 1,882

2,597 8.03 1,028 8.22 1,638 7.92 365 10.95 160 11.39 208 10.62 2,882 8.36

53.85% 65.07% 47.13% 51.04% 67.47% 38.64% 53.53%

9.00%

9.07%

Before COVID Vaccine Availability During COVID Vaccine Availability

11.97% 7.23% 3.37% 4.22% 2.73% 8.36%

10.46% 8.24% 7.25% 7.83% 6.82% 8.86%

Had Metformin

386 166 220

Before COVID Vaccine Availability During COVID Vaccine Availability

Total

3,396

Table 1: Admission and Vaccine statistics in T2DM patients on Metformin therapy vs. Not on Metformin therapy

123

2024 Research Recognition Day