Background <p>The present study aimed to investigate the effects of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on insulin resistance and weight reduction through advanced glycation end-product modulation in patients newly diagnosed with type 2 diabetes mellitus.</p> Methods <p>This study was designed as a 12-week, randomized, controlled, parallel trial. A total of 120 patients with type 2 diabetes were selected and divided into two distinct groups: group I, patients who received gliclazide in combination with metformin, and group II, patients who received vildagliptin in combination with metformin. The percentage change in body weight was estimated along with serum advanced glycated end-product levels, glycated hemoglobin (HbA1c), and insulin resistance.</p> Results <p>Upon completing the study period, when vildagliptin was added to metformin instead of gliclazide, the results demonstrated a significant improvement in insulin resistance, a downregulation of serum levels of advanced glycation end products, glycated hemoglobin, and a decrease in body weight.</p> Conclusion <p>Vildagliptin showed a promising effect on improving type 2 diabetes mellitus–related complications by reducing advanced glycated end-product levels and insulin resistance. Additionally, vildagliptin reveals a favorable impact on weight reduction and glycated hemoglobin values.</p> Graphical Abstract <p></p>