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Objective: To determine the clinical efficacy of linagliptin combined with irbesartan in patients with diabetic nephropathy (DN)., Methods: Seventy-two patients who were admitted to our department of endocrinology in our hospital during January 2018 and June 2019 were randomly divided into a control group (administered with irbesartan only, n=36) and a treatment group (treated with irbesartan and linagliptin, n=36). The course of treatment lasted for three months. FBG (fasting blood glucose), 2hPBG (2h postprandial blood sugar), HbA1C (hemoglobin A1c), Cys-C (cystatin C), SCr (serum creatinine), BUN (blood urea nitrogen), UACR (urine albumin-to-creatinine ratio), CRP (C-reactive protein), IL-6 (interleukin-6), and SOD (superoxide dismutase) were tested pre- and post-treatment to evaluate the clinical efficacy and adverse effects of the two treatment plans after three months of treatment., Results: Compared with the pre-treatment levels, FBG, 2hPBG, HbA1c, Cys-C, SCr, BUN, UACR, CRP, IL-6, and SOD in both groups were significantly improved following the three-month treatment (P<0.05, respectively). Post-treatment levels of FBG, 2hPBG, HbA1c, Cys-C, SCr, BUN, UACR, CRP, and IL-6 in the treatment group were significantly lower than in the control group (P<0.05, respectively), while the treatment group exhibited a higher level of SOD compared with the control group (P<0.05). No serious adverse reaction occurred in either group (P>0.05)., Conclusion: Combined-modality treatment with linagliptin and irbesartan shows favorable clinical efficacy in treating diabetic nephropathy as it effectively protects the kidneys and improves kidney function by inhibiting inflammatory and oxidative stress responses., Competing Interests: Conflicts of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)