Metformin Not Associated With Increased Risk of IBD

Metformin, a glucose lowering drug primarily used in the older population, does not increase the risk of inflammatory bowel disease (IBD).

A team, led by Kristine H. Allin, Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Department of Clinical Medicine, Aalborg University, examined whether metformin protects against the development of IBD in older patients.

The Drug

Metformin, which is primarily used in older patients, is known for pleiotropic effects that include anti-inflammatory properties and effects on gut microbiome.

In the Danish nationwide, population-based cohort, the investigators conducted a nested case-control study using a new-user active comparator design. The team matched each patient with IBD with 10 healthy controls with similar age, sex, and duration of follow-up.

They then estimated odds ratios of IBD using conditional logistic regression and made various adjustments including educational level, other immune-mediated inflammatory diseases, and the use of dipeptidyl peptidase (DPP)-4 inhibitors and statins.

The control group included 302,863 participants who did not have IBD who were treated with oral glucose-lowering drugs. Of this group, 1271 patients developed IBD.

The mean age at IBD diagnosis was 66 years.

Associations With IBD

There was no association found between ever using metformin and the risk of either IBD (aOR, 0.95; 95% CI, 0.78–1.15), Crohn’s disease (aOR, 0.87; 95% CI 0.60–1.26), or ulcerative colitis (aOR, 1.04; 95% CI 0.83–1.31).

This was also true for the cumulative dose of metformin or the treatment duration with metformin associated risk of IBD.

“In this population-based study, we report that despite anti-inflammatory effects and a notable impact on the gut microbiome, metformin use is not associated with reduced risk of older onset IBD,” the authors wrote.

Metformin

Another advantage of metformin, discovered earlier this year, is that the treatment may reduce the mortality rate from influenza, particularly for patients with obesity.

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.

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.

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).

The study, “Metformin use is not associated with reduced risk of older onset inflammatory bowel disease: a Danish nationwide population-based study,” was published in the Journal of Gastroenterology.