Dipeptidyl peptidase 4 (DPP4) inhibitors are increasingly being used to treat patients with type 2 diabetes mellitus (T2DM); however, new research suggests that this class of drugs could increase the risk of incident inflammatory bowel disease (IBD).

“For the present study, we were interested in assessing the impact of DPP4 inhibitors on autoimmunity, given the role of DPP4 in immune function,” explains lead author Devin Abrahami. The researchers used data from Clinical Practice Research Datalink, a primary care database from the UK, to identify 141,170 patients with T2DM who started antidiabetic treatment between 1 January 2007 and 31 December 2016. They then compared the use of DPP4 inhibitors with use of other antidiabetic agents, taking into account additional factors such as smoking, alcohol use and BMI.

Over 552,413 person-years of follow-up, 208 cases of incident IBD were recorded. Adjusted hazard ratios revealed that use of DPP4 inhibitors was associated with a 75% increased risk of IBD. The hazard ratios increased with duration of use, peaking after 3–4 years and decreasing after >4 years. The researchers conducted several secondary analyses, and the findings remained consistent.

Although the absolute risk of IBD with use of DPP4 inhibitors is low, the authors caution that clinicians should consider not prescribing these agents to patients who are already at increased risk of IBD and that gastrointestinal symptoms in patients receiving DPP4 inhibitors should be closely monitored.

“Additional research is needed to replicate our findings,” states senior author Laurent Azoulay. “However, our findings open the doors to investigate the effect of these drugs on other autoimmune conditions where DPP4 is thought to be involved.”