Diabetic nephropathy (DN) is one of the most important causes that leads to end‑stage renal disease and the efficacy of strategies currently available for the prevention of DN remains unsatisfactory. Sitagliptin (SIT), which is a dipeptidyl peptidase‑4 inhibitor, exhibited a modest beneficial effect on glycated hemoglobin levels and is capable of ameliorating renal ischemia reperfusion injury. By determining the expression of transforming growth factor‑β1 (TGF‑β1), connective tissue growth factor (CTGF), collagen type IV (ColIV) and fibronectin (FN) levels in high glucose‑cultured glomerular mesangial cells (MCs), the present study aimed to assess the anti‑proliferative and anti‑fibrotic effects of SIT on the therapeutic potential for the prevention of DN and its mechanism. Specifically, cell proliferation was determined via cell counting kit‑8 assay, and the expression levels of TGF‑β1 and CTGF mRNA were detected by reverse transcription polymerase chain reaction analysis. Furthermore, the secretion of TGF‑β1, CTGF, ColIV and FN proteins was measured via enzyme‑linked immunosorbent assays. The results demonstrated that high glucose induced the proliferation of MCs and enhanced the expression of TGF‑β1, CTGF, ColIV and FN. Furthermore, treatment with SIT inhibited cell proliferation and the expression of TGF‑β1, CTGF, ColIV and FN induced by high glucose. In conclusion, SIT inhibits cell proliferation and the expression of the major extracellular matrix proteins induced by high glucose, indicating its value for treating or relieving DN.

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