Background: Teneligliptin, a new DPP4 inhibitor, was approved in India in 2019 and has been shown to improve blood glucose and lipid profile. The purpose of this study was to compare the efficacy and safety metformin with teneligliptin combination versus metformin with glimepiride which is the most common combination prescribed in diabetes. Material and Method: This was an interventional, open-label, randomized trial on T2DM patients presenting to the OPD of the general medicine department at AIIMS Patna. A total of 326 patients were enrolled with a 10% dropout rate then they were randomly assigned to one of two groups: Group A (163) received metformin (500 mg) with teneligliptin (20 mg), while Group B (163) received metformin (500 mg) with glimepiride (1 mg). Both combinations were once daily and were evaluated to improve glucose and lipids at regular intervals. ADRs of both groups were also recorded. Result: The comparison of blood glucose indices between the two groups was significant at the end of the six-month treatment period. HbA1c (p=0.02), FBG (p=0.02), and PPBG (p=0.03). When the group’s lipid profiles were examined at the end of treatment, there was a significant difference seen in HDL (p=0.001), LDL (p=0.12), and TG (p=0.01). The common ADRs were nausea in both groups while gastritis and weight loss were most common in Group A and hypoglycemia and diarrhea were mostly seen in Group B. Conclusion: In this study, both combinations were well tolerated, but patients who received metformin and teneligliptin showed better control of their lipid profile and glycemic index.