Metformin Reduces Mortality Rate for Influenza Patients With Obesity

Obesity was added to the list of risk factors for influenza in 2009.

Metformin is a promising treatment option for influenza, particularly for patients with obesity.

A team, led by Tammy H. Cummings, Dorn Research Institute, Columbia Veterans Affairs Health Care System, evaluated metformin as a treatment for managing influenza in patients with obesity.

The Risk

Obesity has been a known risk factor for influenza since the 2009 influenza pandemic by leading to a chronic inflammatory status with T-cell dysfunction.

“The identification of obesity as an independent risk factor for influenza morbidity and mortality is of significant concern because there are nearly 500 million individuals with obesity worldwide,” the authors wrote.

While influenza vaccination has had an impact at stopping the spread of the virus, even vaccinated individuals with obesity have higher risks of influenza and influenza-like illnesses compared to vaccinated healthy adults, despite equal serologic responses to the vaccine.

Recent preclinical research has shown metformin, a common oral treatment for diabetes, could help reduce influenzas activity by restoring T-cell function and improve the immune response.

VA Data

In the study, the investigators used national claims data from the VA Informatics and Computing Infrastructure (VNCI) database to identify patient-level data on demographics, administrative claims, and pharmacy dispensation.

Overall, 3551 patients met the inclusion criteria between January 2011 and December 2019 were included in the final analysis. Each patient was at least 18 years, had greater than 1 year between VA enrollment and index, had an influenza vaccine in the 9 months prior to index, had a body mass index greater than or equal to 30, were diagnosed in a primary care or emergency department setting, and were not transferred to an emergency department.

They developed a cohort of patients with laboratory confirmed diagnosis of influenza with an additional diagnosis of fever, cough, influenza, or acute upper respiratory infection in an outpatient setting.

The investigators sought outcomes of death following the diagnosis of influenza. They also formed cohorts using diabetes status and metformin exposure before the positive influenza diagnosis and estimated hazard ratios for mortality using a Cox proportional hazards model adjusting for baseline covariates.

Finally, they conducted a sub-analysis utilizing propensity score matching and utilized a greedy nearest neighbor algorithm to match non-metformin diabetic controls (n = 493) and non-diabetic controls (n = 1461) to diabetic patients receiving metformin (n = 1597).

Metformin and the Mortality Rate

The results show diabetic patients with metformin had a lower mortality rate (aHR, 0.78; 95% CI, 0.609-0.999) compared to the non-diabetic patient cohort. The mortality rate for diabetic patients treated with metformin was 12.73%, compared to 19.41% for the non-metformin diabetic cohort.

However, there was not a statistically significant difference between non-diabetic patients and diabetic patients without metformin (aHR, 1.046; 95% CI, 0.781-1.400).

In addition, the investigators found consistent results with the primary analysis in the propensity score matched cohorts.

“Obesity is an independent risk factor for increased morbidity and mortality in response to influenza infection,” the authors wrote. “Our results demonstrated a decreased mortality rate for patients with obesity diagnosed with influenza and treated with metformin. Further research on metformin is warranted for the treatment of influenza.”

The study, “Patients with Obesity and a History of Metformin Treatment Have Lower Influenza Mortality: A Retrospective Cohort Study,” was published online in Pathogens.