Drug used to treat diabetes could also be effective treatment for inflammatory bowel disease

U of A researcher Karen Madsen is on the path towards a novel treatment for inflammatory bowel syndrome (IBD) thanks to some help from an unexpected place.

Madsen—the director of the Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, with a long history of research on gastrointestinal issues—has found that a drug called empagliflozin (EMPA), commonly used to treat diabetes, also reduces inflammation in the bowels and contributes to healing of damaged tissue in mice. Madsen was recently awarded a research grant from Crohn's and Colitis Canada to support this preliminary work, which could lead to human trials of the drug for IBD within a year or two.

“I was amazed at the results because I haven't found anything that was effective in healing tissue damage in our animal models of IBD,” said Madsen, who is also a member of the Women and Children’s Health Research Institute. “When I treated them with EMPA, there was a dramatic improvement in intestinal inflammation. I haven't seen that with any other drugs that I’ve tried.”

“This is such good preliminary evidence, and I’m really excited to see if we can move these into IBD patients, because I think it's going to benefit them dramatically.”

Currently, patients living with IBD have limited options when it comes to treatments and many of those treatments come with significant side-effects, Madsen said. One treatment option is immunosuppressant drugs such as steroids, which can put the body at risk of other infections. Another common treatment is the use of biologics—medicines that target specific proteins in the body that cause inflammation. However, these are usually administered intravenously, which can bring other risks to patients—particularly older ones—over time.

Further, only about 30 to 40 per cent of patients living with IBD will respond to current drugs, Madsen said. And those who do respond at first begin to lose that response over time. EMPA, however, interacts with the immune system in a completely different way.

“EMPA doesn't suppress the immune system,” Madsen said. “What it appears to do is change the immune cells from an inflammatory state to an anti-inflammatory state by changing the cell’s metabolism.”

Serendipitous friends

EMPA would not even have been considered as an option for treating IBD were it not for a conversation with colleague and friend Jason Dyck, a professor in the Department of Pediatrics, Madsen said.

“From clinical trials of the drug for diabetics, his team was aware that it also produced a cardio-protective effect,” Madsen said. “When they investigated it, they discovered that EMPA was reducing inflammation, which led Jason to think it could be effective for IBD. So then he came to me and offered it up.”

“I think this shows that it's really important to talk to other people about your work,” she added. “Having interactions between different areas of research leads to amazing things.”

“That’s one of the great things about working at the U of A,” agreed Dyck. “Most researchers are very open to collaborating. This is key to making rapid advances and speaks to the importance of collaboration being instrumental for groundbreaking research discoveries.”

The next step for Madsen was to recruit Leo Dieleman, a gastroenterologist involved in the
care of IBD patients, to help further explore the process of how EMPA changes immune cells from inflammatory to anti-inflammatory and develop a proof-of-concept model for the drug using human immune cells. That work will hopefully lead to human trials of the drug in treating IBD, Madsen said.

“Once I show that immune cells will respond in predictable ways to EMPA, then I envision going into a small proof-of-principle human trial within a year or two,” she said. “The benefit of EMPA is it is already approved for use, so this is a re-purposing of the drug, which is relatively simple compared to getting a new drug on the market.”