Abstract
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.
Highlights
Dipeptidyl peptidase-4 inhibitors (DPP4i) are oral agents used for the pharmacological treatment of adults with type 2 diabetes mellitus (T2DM)
Duration of diabetes was significantly higher in the dipeptidyl peptidase-4 inhibitors (DPP4i) group compared to those who did not receive the treatment (p < 0.01). eGFR was significantly reduced in T2DM patients treated with
The present data do not suggest any major effect of DPP4i on oxidative stress, as explored through the measurement of several circulating biomarkers
Summary
Dipeptidyl peptidase-4 inhibitors (DPP4i) are oral agents used for the pharmacological treatment of adults with type 2 diabetes mellitus (T2DM). Several clinical trials demonstrated that these agents are effective in reducing glycated hemoglobin (HbA1c) with a low risk of hypoglycemia and neutral effects on weight, compared to sulphonylureas [2,3,4]. A meta-analysis of short and medium-term trials with metabolic endpoints, showed that the treatment with DPP4i was associated with reduced incidence of major adverse cardiovascular events (MACE) and all-cause mortality [5]. Trials with cardiovascular events as major endpoints, showed a neutral effect of DPP4i with respect to the incidence of MACE in T2DM patients with cardiovascular disease [6,7,8]. A post hoc analysis from the SAVOR-TIMI 53, found a moderate increase in the risk of hospitalization due to hearth failure with saxagliptin compared to Antioxidants 2020, 9, 233; doi:10.3390/antiox9030233 www.mdpi.com/journal/antioxidants
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