Dipeptidyl Peptidase 4 Inhibitors Decrease the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis C Infection and Type 2 Diabetes Mellitus: A Nationwide Study in Taiwan

Introduction: Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors) are incretin-based oral antidiabetic drugs. Previous studies have shown an association between increased plasma activity of DPP-4 and chronic hepatitis C virus (HCV) infection. Dipeptidyl peptidase 4 inhibitors may be associated with preventing the development of chronic HCV infection. The aim of this study was to investigate whether the use of DPP-4 inhibitors is associated with a decreased risk of hepatocellular carcinoma (HCC) in patients with diabetes mellitus (DM) and chronic HCV infection.Methods: In this retrospective cohort study, we enrolled patients with type 2 diabetes and chronic HCV infection from the National Health Insurance Research Database (NHIRD) in Taiwan. The patients were divided into two groups (DPP-4 inhibitor cohort and non-DPP-4 inhibitor cohort) according to whether or not they received DPP-4 inhibitor treatment.Results: Multivariate Cox proportional hazard regression analysis showed a significantly lower risk of HCC in the patients who took DPP-4 inhibitors compared to those who did not. Kaplan-Meier survival analysis demonstrated a significantly higher HCC-free rate in the DPP-4 inhibitor cohort than in the non-DPP-4 inhibitor cohort.Conclusion: The use of DPP-4 inhibitors was associated with a lower risk of HCC in patients with type 2 DM and chronic HCV infection.

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Effect of Dipeptidyl-Peptidase 4 Inhibitors on Circulating Oxidative Stress Biomarkers in Patients with Type 2 Diabetes Mellitus

Antioxidants ◽

10.3390/antiox9030233 ◽

2020 ◽

Vol 9 (3) ◽

pp. 233

Author(s):

Elisabetta Bigagli ◽

Cristina Luceri ◽

Ilaria Dicembrini ◽

Lorenzo Tatti ◽

Francesca Scavone ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Propensity Score ◽

Oxidative Damage ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase 4 ◽

Dipeptidyl Peptidase 4 Inhibitors

Pre-clinical studies suggested potential cardiovascular benefits of dipeptidyl peptidase-4 inhibitors (DPP4i), however, clinical trials showed neither beneficial nor detrimental effects in patients with type 2 diabetes mellitus (T2DM). We examined the effects of DPP4i on several circulating oxidative stress markers in a cohort of 32 T2DM patients (21 males and 11 post-menopausal females), who were already on routine antidiabetic treatment. Propensity score matching was used to adjust demographic and clinical characteristics between patients who received and who did not receive DPP4i. Whole-blood reactive oxygen species (ROS), plasma advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), carbonyl residues, as well as ferric reducing ability of plasma (FRAP) and leukocyte DNA oxidative damage (Fpg sites), were evaluated. With the exception of Fpg sites, that showed a borderline increase in DPP4i users compared to non-users (p = 0.0507), none of the biomarkers measured was affected by DPP4i treatment. An inverse correlation between estimated glomerular filtration rate and AGEs (p < 0.0001) and Fpg sites (p < 0.05) was also observed. This study does not show any major effect of DPP4i on oxidative stress, assessed by several circulating biomarkers of oxidative damage, in propensity score-matched cohorts of T2DM patients.

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