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

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

Author information

1Division of Endocrinology and Metabolism, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565 Japan.
2Division of Preventive Cardiology, National Cerebral and Cardiovascular Center, Suita, Osaka Japan.



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.


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.


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.


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).


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

[Available on 2019-09-28]

Conflict of interest statement

The authors declare that they have no conflict of interest.All subjects provided written informed consent.The study was approved by the ethics committee of National Cerebral and Cardiovascular Center (approved at December 9, 2013, approval number: M25-095) and performed in accordance with Helsinki Declaration of 1964 and later versions. This study was registered under UMIN (ID UMIN 000015308).

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