Title: Comparison of Glimepiride dosing and blood sugar levels in Type 2 Diabetes Mellitus - A Meta-Analysis Author: Sheema Khan, Master of Science Clinical Research, 2019 Thesis Directed by: Dr. Andrew Bean, PhD, Dean of Graduate College Background: Glimepiride, a sulfonylurea drug, is widely used to manage blood glucose in Type 2 Diabetes Mellitus (T2DM). Recommended dosages range from 1 to 8 mg daily, typically administered alongside Metformin. Dose escalation, though common, poses risks of hypoglycemia and cardiovascular concerns. Objective: To conduct a meta-analysis of randomized clinical trials comparing the efficacy of 2 mg versus 4 mg Glimepiride as add-on therapy with Metformin in T2DM patients aged 18 and above. Primary outcome measured was change in HbA1c levels; secondary outcomes included BMI, Fasting Plasma Glucose (FPG), lipid levels, lipid subtypes, and frequency of hypoglycemic episodes. Methods: Fifty-one RCTs were initially identified from databases such as PubMed and Scopus, with 11 studies meeting inclusion criteria (2 mg group: 693 subjects; 4 mg group: 666 subjects). Comprehensive meta-analysis using "Comprehensive Meta-Analysis (CMA)" software was performed, utilizing difference in means and standardized difference in means to assess outcomes. Results: Both 2 mg and 4 mg doses of Glimepiride significantly reduced HbA1c levels, with the 2 mg dose showing a greater reduction. Subgroup analyses indicated significant heterogeneity among studies. FPG reduction was statistically significant for both doses, while BMI changes and lipid levels did not show significant associations with dose. Hypoglycemia risk was lower with the 2 mg dose compared to 4 mg. Conclusion: The meta-analysis supports the efficacy of both Glimepiride doses in reducing HbA1c levels, with the 2 mg dose demonstrating superior results. Significant associations were observed between FPG reduction and Glimepiride dose, while other outcomes showed mixed results. These findings suggest potential benefits of initiating treatment with the 2 mg dose to minimize hypoglycemia risk and achieve effective glycemic control in T2DM patients. Limitations: Limitations include the lack of direct comparative studies between 2 mg and 4 mg doses and high heterogeneity among included trials. Larger randomized trials are recommended to validate these findings and guide clinical practice.