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Dipeptidyl Peptidase-4 Inhibitors and the Risk of Pancreatitis in Patients with Type 2 Diabetes Mellitus: A Population-Based Cohort Study.

ABSTRACT: Background:Information on the risk of acute pancreatitis in patients receiving dipeptidyl-peptidase IV inhibitors (DPP-4i) is limited and controversial. One study suggested that the differences in findings between these meta-analyses were attributed to whether they included large randomized control trials with cardiovascular outcomes or not. The aim of our study was to determine whether the use of DPP-4i increases the risk of acute pancreatitis compared with sulfonylurea (SU) and whether the risk is higher in patients with underlying cardiovascular disease (CVD). Methods:A population-based cohort study was performed using Korean National Health Insurance Service-National Sample Cohort data. We included 33,395 new users of SU and DPP-4i from 1 January 2008 to 31 December 2015. SU-treated patients and DPP-4i-treated patients were matched by 1 : 1 propensity score matching. We used Kaplan-Meier curves and Cox proportional hazards regression analysis to calculate the risk of acute pancreatitis. Results:The hazard ratio (HR) of hospitalization for acute pancreatitis was 0.642 (95% confidence interval (CI): 0.535-0.771) in DPP-4i-treated patients compared with SU-treated patients. The HR of DPP-4i use was also lower than that of SU use in patients without underlying CVD (HR: 0.591; 95% CI: 0.476-0.735) but not in patients with underlying CVD (HR: 0.727; 95% CI: 0.527-1.003). Conclusion:Our findings suggest that DPP-4i is less likely to cause drug-induced pancreatitis than SU. This finding was not evident in patients with CVD, but DPP-4i was not more likely to induce pancreatitis in these patients than SU was.

SUBMITTER: Kim YG

PROVIDER: S-EPMC5914097 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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 v 34.5 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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Dipeptidyl Peptidase-4 Inhibitors and the Risk of Pancreatitis in Patients with Type 2 Diabetes Mellitus: A Population-Based Cohort Study.

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