The Oral Dipeptidyl-Peptidase-4 Inhibitor Sitagliptin Increases Circulating Levels Of Stromal-Derived Factor-1 Alpha

Abstract

AbstractRecent studies have demonstrated that stromal derived factor-1α (SDF-1α) is a substrate of dipeptidyl-peptidase-4 (DPP-4) inhibitors. It has also been shown that SDF-1α shares anti-apoptotic as well as nephroprotective properties and exerts a beneficial effect in the cardiovascular system. Therefore, the aim of this study was to estimate the effect of treatment with the DDP-4 inhibitor sitagliptin on SDF-1α levels in subjects with type 2 diabetes mellitus (T2D). Overall, 32 patients (16 males) with T2D, mean age (±SD) 67.2±8.3 years, HbA1c 6.4±0.5%, body-mass index (BMI) 29.1±4.9 Kg/m2, T2D duration 8.5±4.0 years receiving metformin monotherapy (17 participants) or metformin plus sitagliptin (15 participants) without known cardiovascular disease were enrolled. Patients on metformin plus sitagliptin exhibited higher plasma levels of SDF-1α compared with those on metformin monotherapy (19.6±4.1 versus 6.9±1.3 pg/ml, respectively, p=0.01). Multivariate regression analysis after controlling for age, sex, body-mass index, smoking, arterial hypertension, dyslipidaemia and other confounders showed that SDF-1α levels were positively correlated with DPP-4 inhibitor treatment (beta=0.91, p=0.001), and negatively with T2D duration (beta=− 0.42, p=0.05), ΗDL-cholesterol levels (beta=− 0.46, p=0.02) and HbA1c (beta=− 0.41, p=0.05). In conclusion, these results suggest that sitagliptin treatment may exert a favourable effect on SDF-1α levels.