Impact of Sitagliptin on Neprilysin and Glycemic Control in Newly Diagnosed Type 2 Diabetes Patients

BACKGROUND Dipeptidyl peptidase-4 (DPP-4) and neprilysin (NEP) regulate glucose metabolism through incretin activity. While DPP-4 inhibitors have established benefits in glycemic control, the precise role of NEP in metabolic regulation remains unclear. This study assessed the effect of sitagliptin therapy on serum neprilysin levels and its association with glycemic and metabolic parameters in patients with newly diagnosed type 2 diabetes. MATERIAL AND METHODS Thirty-five patients with newly diagnosed type 2 diabetes were included in this prospective study. Sitagliptin (100 mg/day) was administered for 3 months. Serum neprilysin levels, body mass index (BMI), waist circumference, and glycemic parameters were measured at baseline and after 3 months. A multivariable regression analysis was conducted to assess the relationship between neprilysin levels and metabolic parameters. RESULTS Serum neprilysin levels remained unchanged after sitagliptin therapy (p=0.789). However, neprilysin changes were significantly associated with BMI change (ß=-0.0003, p=0.001), while no significant relationship was found with waist circumference (p=0.464) or homeostasis model assessment (HOMA) levels (p=0.383). CONCLUSIONS Sitagliptin therapy significantly improves glycemic control and promotes weight loss without affecting serum neprilysin levels. The significant association between neprilysin changes and BMI suggests that neprilysin may have a more direct role in body composition rather than glucose homeostasis.