Background and aim: Defects in insulin secretion and action are metabolic diseases termed diabetes mellitus. This research aimed to compare the efficacy of glimepiride plus metformin versus teneligliptin plus metformin therapy in patients with type 2 diabetes mellitus. Method: A prospective observational study was conducted on 48 patients suffering from type 2 diabetes mellitus in the outpatient department. The participants were divided into two groups (each group consists of 24 participants). The first group received glimepiride plus metformin, and the second group received teneligliptin plus metformin. The patient's FBS and PPBS levels were monitored for consecutive months. Results: A total of 24 patients with type 2 diabetes mellitus participated in this study in each group. Comparing the FBS levels of both groups, more reduction was found in the teneligliptin plus metformin therapy, and a significant reduction of the PPBS level was also found in the teneligliptin plus metformin therapy than in the glimepiride plus metformin therapy. Conclusion: The findings of this research indicate that teneligliptin plus metformin therapy was effective and had better efficacy than glimepiride plus metformin in reducing the glycaemic parameter in patients with type 2 diabetes mellitus.