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      Emergence of inflammatory bowel disease during treatment with sitagliptin Translated title: Debut de enfermedad inflamatoria intestinal durante el tratamiento con sitagliptina

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          Abstract

          SUMMARY We present one clinical case of diagnosed inflammatory bowel disease, as a probable adverse reaction to sitagliptin. Sitagliptin is a dipeptidylpeptidase (DPP)-4 inhibitor authorised for the type II diabetes mellitus treatment in adult patients who do not achieve good blood glucose control and if other therapeutic alternatives are not correctly tolerated. In addition to the DPP-4 role in the gastric hormones release and glucose homeostasis, the DPP-4 involvement in the inflammatory response is known. However, the relationship between inflammatory bowel disease (IBD) and inhibition of PPD-4 is controversial. On the one hand, the T lymphocytes of patients with this pathology seem to express high levels of the enzyme DPP-4, so their inhibition could be associated with a decrease in the activity of IBD. On the other hand, in a cohort study of patients treated with oral antidiabetics an increased risk of IBD was observed and there are different published cases of IBD occurrence during the use of sitagliptin.

          Translated abstract

          RESUMEN Presentamos un caso de debut de enfermedad inflamatoria intestinal (EII) como probable reacción adversa a la administración de sitagliptina. Sitagliptina es un inhibidor de la dipeptidilpeptidasa 4 (DPP-4) autorizado para el tratamiento de la diabetes mellitus tipo II en pacientes adultos que no consiguen buen control de la glucemia, o si el resto de alternativas terapéuticas no son bien toleradas. Además del papel de la DPP-4 en la liberación de hormonas gástricas y en la homeostasis de la glucosa, se sabe que esta enzima también está implicada en la respuesta inflamatoria. Sin embargo, la relación entre la EII y la inhibición de la DPP-4 es controvertida. Por un lado, los linfocitos T de los pacientes con esta patología parecen expresar altos niveles de la enzima DPP-4, por lo que su inhibición se podría asociar a un descenso en la actividad de la EII. Por otro lado, en un estudio de cohortes de pacientes tratados con antidiabéticos orales se observó un aumento del riesgo de EII y existen diferentes casos publicados de aparición de IBD durante el uso de sitagliptina.

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          Most cited references9

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          Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system.

          CD26/DPP4 (dipeptidyl peptidase 4/DP4/DPPIV) is a surface T cell activation antigen and has been shown to have DPP4 enzymatic activity, cleaving-off amino-terminal dipeptides with either L-proline or L-alanine at the penultimate position. It plays a major role in glucose metabolism by N-terminal truncation and inactivation of the incretins glucagon-like peptide-1 (GLP) and gastric inhibitory protein (GIP). In 2006, DPP4 inhibitors have been introduced to clinics and have been demonstrated to efficiently enhance the endogenous insulin secretion via prolongation of the half-life of GLP-1 and GIP in patients. However, a large number of studies demonstrate clearly that CD26/DPP4 also plays an integral role in the immune system, particularly in T cell activation. Therefore, inhibition of DPP4 might represent a double-edged sword. Apart from the metabolic benefit, the associated immunological effects of long term DPP4 inhibition on regulatory processes such as T cell homeostasis, maturation and activation are not understood fully at this stage. The current data point to an important role for CD26/DPP4 in maintaining lymphocyte composition and function, T cell activation and co-stimulation, memory T cell generation and thymic emigration patterns during immune-senescence. In rodents, critical immune changes occur at baseline levels as well as after in-vitro and in-vivo challenge. In patients receiving DPP4 inhibitors, evidence of immunological side effects also became apparent. The scope of this review is to recapitulate the role of CD26/DPP4 in the immune system regarding its pharmacological inhibition and T cell-dependent immune regulation.
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            Dipeptidyl peptidase-4 inhibitors in type 2 diabetes may reduce the risk of autoimmune diseases: a population-based cohort study.

            Dipeptidyl peptidase-4 (DPP4), also known as CD26, is a transmembrane glycoprotein that has a costimulatory function in the immune response. DPP4 inhibitors (DPP4i) are oral glucose-lowering drugs for type 2 diabetes mellitus (T2DM). This study evaluated the risk of incident rheumatoid arthritis (RA) and other autoimmune diseases (AD) such as systemic lupus erythematosus, psoriasis, multiple sclerosis and inflammatory bowel disease, associated with DPP4i in patients with T2DM.
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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.
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                Author and article information

                Journal
                ofil
                Revista de la OFIL
                Rev. OFIL·ILAPHAR
                Organización de Farmacéuticos Ibero-Latinoamericanos (Madrid, Madrid, Spain )
                1131-9429
                1699-714X
                2020
                : 30
                : 3
                : 251-252
                Affiliations
                [2] Sevilla orgnameHospital de Valme orgdiv1Servicio Endocrinología y Nutrición España
                [1] Sevilla orgnameHospital de Valme orgdiv1Servicio Farmacia España
                Article
                S1699-714X2020000300251 S1699-714X(20)03000300251
                10.4321/s1699-714x2020000300016
                2af61ee3-fe01-476a-96f4-bef3975209ca

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 03 August 2019
                : 10 June 2019
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 9, Pages: 2
                Product

                SciELO Spain

                Categories
                Clinical Cases

                enfermedad de Crohn,Crohn's disease,Sitagliptina,adverse effect,reacción adversa,Sitagliptin

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