Effect of linagliptin on oxidative stress markers in patients with type 2 diabetes: a pilot study

Diabetol Int. 2018 Sep 28;10(2):148-152. doi: 10.1007/s13340-018-0376-9. eCollection 2019 Apr.


Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used for the treatment of type 2 diabetes and have been previously shown to prevent diabetic renal injury via various mechanisms, including the attenuation of oxidative stress. Therefore, we hypothesized that linagliptin, a DPP-4 inhibitor, attenuates oxidized stress and diabetic renal injury.

Methods: In total, 30 patients with type 2 diabetes who were undergoing treatment with linagliptin (5 mg) during the 3-month study period were enrolled. Oxidative stress markers [serum malondialdehyde-modified LDL (MDA-LDL) and urinary 8-hydroxydeoxyguanosine (8-OHdG)], an inflammatory marker (high-sensitive CRP), urinary albumin excretion, estimated GFR, and a urinary tubulointerstitial injury marker [urinary liver-type fatty acid-binding protein (L-FABP)] were evaluated at baseline and after 3 months of treatment.

Results: Following linagliptin treatment, serum MDA-LDL, serum HbA1c, and urinary L-FABP levels significantly decreased, while urinary 8-OHdG tended to decrease. In contrast, 1,5-AG levels increased, and high-sensitive CRP and urinary albumin excretion remained unchanged.

Conclusion: In this study, we demonstrated that linagliptin partially attenuated oxidative stress. We also demonstrated that linagliptin treatment reduced urinary L-FABP excretion, suggesting that renal tubule-interstitial injury may be attenuated by linagliptin (UMIN 000015308).

Keywords: DPP-4 inhibitor; Diabetic kidney disease; Oxidative stress; Tubulointerstitial injury.