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Use of DPP-4 inhibitors associated with increased risk of IBD

Relative risk of IBD 75% higher in people taking these diabetes drugs – but absolute risk is low

Louise Prime

Thursday, 22 March 2018

The relative risk of developing inflammatory bowel disease (IBD) is 75% higher among people with type 2 diabetes taking dipeptidyl peptidase-4 inhibitors (DPP-4), research using UK general practice data has shown. The researchers behind the study* – published today in the BMJ – stressed that the absolute risk is small and more research is needed to replicate their results, but they added that physicians should be aware of this possible association and perhaps avoid prescribing the drugs for high-risk patient.

A research team from Montreal, Canada, pointed out that the effect of the DPP-4 enzyme in autoimmune diseases such as IBD is not well understood; low concentrations of the DPP-4 enzyme have been associated with increased IBD activity, although the direction of this association remains unclear – and no observational studies have investigated the association between the use of DPP-4 inhibitors and the incidence of IBD. So they conducted a population-based cohort study to find out more.

They analysed data from more than 700 general practices contributing data to the UK Clinical Practice Research Datalink, for a cohort of 141,170 adults who had started antidiabetes drugs between 1 January 2007 and 31 December 2016, with follow-up until 30 June 2017. They calculated adjusted hazard ratios for incident IBD associated with use of DPP-4 inhibitors overall, by cumulative duration of use, and by time since initiation; they modelled use of DPP-4 inhibitors as a time varying variable and compared their use with that of other antidiabetes drugs.

The researchers reported that 208 incident IBD events occurred during 552,413 person years of follow-up. They found that, overall, use of DPP-4 inhibitors was associated with a significantly increased risk of IBD (hazard ratio, HR 1.75). Hazard ratios gradually increased with longer durations of use, reaching a peak after 3-4 years’ use (HR 2.90), but decreasing after more than four years’ use to a statistically non-significant level (HR 1.45). They found a similar pattern with time since starting these drugs, and also said their findings remained consistent in several sensitivity analyses.

They stressed that although they found a 75% increase in relative risk associated with the use of DPP-4 inhibitors, the absolute risk remained low – there were 53.4 cases per 100,000 person-years in people taking DPP-4 inhibitors, compared with 34.5 cases per 100,000 among those taking other antidiabetic drugs. Also, they noted, theirs was an observational study and so cannot show causation, and confounding factors might lie behind the association.

They concluded: “Although the absolute risk is low, physicians should be aware of this possible association and perhaps refrain from prescribing dipeptidyl peptidase-4 inhibitors for people at high risk (that is, those with a family history of disease or with known autoimmune conditions). Moreover, patients presenting with persistent gastrointestinal symptoms such as abdominal pain or diarrhoea should be closely monitored for worsening of symptoms.”


*Abrahami D, Douros A, Hui Yin, et al. Dipeptidyl peptidase-4 inhibitors and incidence of inflammatory bowel disease among patients with type 2 diabetes: population based cohort study. BMJ 2018; 360:k872 doi: 10.1136/bmj.k872

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