Abstract

Dipeptidyl peptidase-4 inhibitors and incidence of inflammatory bowel diseaseamong patients with type 2 diabetes: population based cohort study

Abrahami D1,2, Douros A1,2,3, Yin H1, Yu OHY1,4, Renoux C1,2,5, Bitton A6,7, Azoulay L1,2,8. BMJ. 2018 Mar 21;360:k872. doi: 10.1136/bmj.k872.
 
     

Author information

1 Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada H3T 1E2.

2 Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada.

3 Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

4 Division of Endocrinology, Jewish General Hospital, Montreal, QC, Canada.

5 Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.

6 Division of Gastroenterology, Department of Medicine, McGill University, Montreal, QC, Canada.

7 McGill University Health Centre, Montreal, QC, Canada.

8 Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada.

Abstract

OBJECTIVE: To assess whether the use of dipeptidyl peptidase-4 inhibitors is associated with the incidence of inflammatory bowel disease in patients with type 2 diabetes.

DESIGN: Population based cohort study.

SETTING: More than 700 general practices contributing data to the United Kingdom Clinical Practice Research Datalink.

PARTICIPANTS: A cohort of 141 170 patients, at least 18 years of age, starting antidiabetic drugs between 1 January 2007 and 31 December 2016, with follow-up until 30 June 2017.

MAIN OUTCOME MEASURES: Adjusted hazard ratios for incident inflammatory bowel disease associated with use of dipeptidyl peptidase-4 inhibitors overall, by cumulative duration of use, and by time since initiation, estimated using time dependent Cox proportional hazards models. Use of dipeptidyl peptidase-4 inhibitors was modelled as a time varying variable and compared with use of other antidiabetic drugs, with exposures lagged by six months to account for latency and diagnostic delays.

RESULTS: During 552 413 person years of follow-up, 208 incident inflammatory bowel disease events occurred (crude incidence rate of 37.7 (95% confidence interval 32.7 to 43.1) per 100 000 person years). Overall, use of dipeptidyl peptidase-4 inhibitors was associated with an increased risk of inflammatory bowel disease (53.4 v34.5 per 100 000 person years; hazard ratio 1.75, 95% confidence interval 1.22 to 2.49). Hazard ratios gradually increased with longer durations of use, reaching a peak after three to four years of use (hazard ratio 2.90, 1.31 to 6.41) and decreasing after more than four years of use (1.45, 0.44 to 4.76). A similar pattern was observed with time since starting dipeptidyl peptidase-4 inhibitors. These findings remained consistent in several sensitivity analyses.

CONCLUSIONS: In this first population based study, the use of dipeptidyl peptidase-4 inhibitors was associated with an increased risk of inflammatory bowel disease. Although these findings need to be replicated, physicians should be aware of this possible association.

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