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

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 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.

SUBMITTER: Abrahami D

PROVIDER: S-EPMC5861502 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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

Abrahami Devin D Douros Antonios A Yin Hui H Yu Oriana Hoi Yun OHY Renoux Christel C Bitton Alain A Azoulay Laurent L

BMJ (Clinical research ed.) 20180321

<h4>Objective</h4>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.<h4>Design</h4>Population based cohort study.<h4>Setting</h4>More than 700 general practices contributing data to the United Kingdom Clinical Practice Research Datalink.<h4>Participants</h4>A cohort of 141 170 patients, at least 18 years of age, starting antidiabetic drugs between 1 January 2007 and 31 December 2016, with ...[more]

PMID: 29563098

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Project description:Type 2 diabetes mellitus is a complex and progressive disease that is showing an apparently unstoppable increase worldwide. Although there is general agreement on the first-line use of metformin in most patients with type 2 diabetes, the ideal drug sequence after metformin failure is an area of increasing uncertainty. New treatment strategies target pancreatic islet dysfunction, in particular gut-derived incretin hormones. Inhibition of the enzyme dipeptidyl peptidase-4 (DPP-4) slows degradation of endogenous glucagon-like peptide-1 (GLP-1) and thereby enhances and prolongs the action of the endogenous incretin hormones. The five available DPP-4 inhibitors, also known as 'gliptins' (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin), are small molecules used orally with similar overall clinical efficacy and safety profiles in patients with type 2 diabetes. The main differences between the five gliptins on the market include: potency, target selectivity, oral bioavailability, long or short half-life, high or low binding to plasma proteins, metabolism, presence of active or inactive metabolites, excretion routes, dosage adjustment for renal and liver insufficiency, and potential drug-drug interactions. On average, treatment with gliptins is expected to produce a mean glycated hemoglobin (HbA1c) decrease of 0.5%-0.8%, with about 40% of diabetic subjects at target for the HbA1c goal <7%. There are very few studies comparing DPP-4 inhibitors. Alogliptin as monotherapy or added to metformin, pioglitazone, glibenclamide, voglibose, or insulin therapy significantly improves glycemic control compared with placebo in adult or elderly patients with inadequately controlled type 2 diabetes. In the EXAMINE trial, alogliptin is being compared with placebo on cardiovascular outcomes in approximately 5,400 patients with type 2 diabetes. In clinical studies, DPP-4 inhibitors were generally safe and well tolerated. However, there are limited data on their tolerability, due to their relatively recent marketing approval. Alogliptin will be used most when avoidance of hypoglycemic events is paramount, such as in patients with congestive heart failure, renal failure, and liver disease, and in the elderly.

Dataset Information

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

Publications

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

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