Montreal—Canadian researchers are warning that use of a specific class of medications to treat diabetes could increase risk of inflammatory bowel disease (IBD).

Results of the observational study published in The BMJ suggest use of the second-line agents dipeptidyl peptidase-4 (DPP-4) inhibitors is associated with higher likelihood of the disease, which causes chronic inflammation of the digestive track.

While the absolute risk is low—researchers urge that their findings be replicated in other studies—they caution that healthcare professionals “should be made aware of this possible association.”

“To our knowledge, this is the first observational study to specifically investigate the association between the use of dipeptidyl peptidase-4 inhibitors and the incidence of inflammatory bowel disease,” study authors write, adding, “This gradual increase in the risk is consistent with the hypothesis of a possible delayed effect of the use of dipeptidyl peptidase-4 inhibitors on the incidence of inflammatory bowel disease. This association remained highly consistent across a variety of sensitivity analyses.”

The pharmaceuticals work by blocking the DPP-4 enzyme, which regulates inflammatory response. Some past research had suggested that lower serum levels of DPP-4 enzyme could be linked to increased disease activity in patients with IBD. That’s why the study team led by McGill University sought to determine whether the use of DPP-4 inhibitors is associated with IBD in patients with type 2 diabetes.

To do that, they analyzed data from the UK’s Clinical Practice Research Database for 141,170 adult patients who were starting antidiabetic drugs between 2007 and 2016. Excluded were patients initially treated with insulin and those with a history of IBD or similar conditions.

Over a monitoring period of 3.5 years, 208 new cases of IBD occurred, an incidence rate of 37.7 per 100,000 person-years. Results indicate that use of DPP-4 inhibitors was associated with 53.4 cases per 100,000 person-years versus 34.5 cases per 100,000 person-years for other anti-diabetic drugs—a 75% increased risk. The study team also identified an increasing association of IBD development with longer durations of DPP-4 inhibitor use, with a peak at 3 to 4 years and then a decline.

The effect appeared to be related to drug class not a specific DPP-4 inhibitor drug, according to the study.

“Although our findings need to be replicated, physicians should be aware of this possible association and perhaps refrain from prescribing DPP-4 inhibitors for people at high risk, such as those with a family history of disease or with known autoimmune conditions,” study authors conclude.

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