Aim: To compare the effectiveness and safety of the glimepiride-metformin combination with the glibenclamide-metformin combination in patients with type-2 diabetes uncontrolled with metformin alone. Material and methods: This research was conducted at the department of pharmacology and followed a randomized, open-label, prospective, comparative design. 80 patients were chosen for the research based on the inclusion criteria mentioned above. The participants were randomly divided into two groups, group A and group B, with 40 participants in each group. Group A was administered a FDC of Glimepiride 1mg and Metformin 500mg orally, once day before meals, for a duration of 6 months. Group B was administered a once-daily oral dosage of FDC Glibenclamide 5mg and Metformin 500mg before meals for a duration of 6 months. Results: Group-A: The mean fasting blood sugar (FBS) levels were 244.87± 42.74, 192.28 ± 42.85, 155.23 ± 33.71, and 126.54 ± 21.68 mg/dl at baseline, 1st, 3rd, and 6th month, respectively. Group-B: The mean fasting blood sugar (FBS) levels were 259.15±48.58, 215.12 ± 47.94, 174.73 ±31.84, and 145.47 ± 20.98 mg/dl at baseline, 1st, 3rd, and 6th month, respectively. Group-A: The mean postprandial blood sugar (PPBS) levels were 309.02 ± 65.23, 246.36 ± 61.88, 192.09 ± 39.54, and 154.28 ± 29.82 mg/dl at baseline, 1st, 3rd, and 6th month, respectively. Group-B: The mean postprandial blood sugar (PPBS) levels were 330.31 ± 63.57, 278.43 ± 56.46, 231.28 ± 42.74, and 193.84 ± 33.98 mg/dl at baseline, 1st, 3rd, and 6th month, respectively. Group-A: The average body weight at baseline, 1st, 3rd, and 6th month was 73.01 ± 11.27 kg, 72.25 ± 10.26 kg, 71.18 ± 10.75 kg, and 70.98 ± 10.98 kg, respectively. Group-B: The mean body weight at baseline, 1st, 3rd, and 6th month was 76.66 ± 11.01 kg, 75.78 ± 11.89 kg, 74.96 ± 11.22 kg, and 73.75 ± 11.64 kg, respectively. Conclusion: In summary, this research has shown the benefits of adding Sulfonylurea to Metformin in Type 2 diabetes patients who have uncontrolled blood sugar levels despite taking Metformin alone. When Metformin 500mg is taken with Glimepiride 1mg, it is more effective than when paired with Glibenclamide 5mg. The occurrence of hypoglycemia is lower while using the combination of Glimepiride and Metformin compared to the combination of Glibenclamide and Metformin. The combination of Metformin with Glimepiride/Glibenclamide has the potential to induce weight loss in persons with type-2 diabetes.