Background: Strict glycemic control delays microvascular and macrovascular complications in type 2 diabetes. Metformin is the first-line therapy, followed by insulin or oral hypoglycemic agents. DPP-4 inhibitors such as teneligliptin offer advantages including lower hypoglycemia risk, good safety profile, and compatibility with other oral agents. Meta-analyses indicate a favorable safety profile for teneligliptin, and it has demonstrated improvements in fasting and postprandial glucose with potential cholesterol-lowering benefits. Voglibose, an α-glycosidase inhibitor, delays glucose absorption and reduces postprandial hyperglycemia. Methods: This prospective randomized controlled study compared the efficacy of teneligliptin and voglibose as add-on therapy in patients with uncontrolled diabetes on metformin 500 mg BD and glimepiride 2 mg OD. Eighty patients aged 40–70 years were divided into two groups (n=40 each). Investigations were performed at baseline, 3 months, and 6 months for FBS, PPBS, and HbA1c. Statistical significance was set at P < 0.05. Results: After 6 months, both groups showed significant reductions in FBS, PPBS, and HbA1c, with teneligliptin demonstrating greater glucose reduction than voglibose. Conclusion: Teneligliptin is more effective than voglibose as a second-line add-on therapy to sulfonylureas, metformin, or insulin. © 2024 Elsevier B.V., All rights reserved.