Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder, which is commonly related to reduced insulin responsiveness and altered appetite-related hormones. In this study, we have evaluated how combined metformin and sulfonylurea therapy affects glycemic indicators and appetite hormones, with special focus on hormone ratios. Sixty participants were involved in the study: 30 diabetic patients receiving combined metformin-sulfonylurea therapy and 30 conditionally healthy individuals serving as controls. Fasting blood samples were collected to assess indicators of glycemic control, lipid profiles, and hormone levels using standard biochemical assays and ELISA. The patient group showed clear increases in fasting glucose, HbA1c, insulin, insulin resistance indices, lipid profile measurements, and leptin levels, whereas the levels of HDL, ghrelin, and adiponectin were markedly decreased compared with the control group (p < 0.001). The results of the study show that T2DM patients continue to have both insulin resistance and poor blood glucose control despite combined metformin-sulfonylurea therapy. Alterations in appetite hormones also reflect underlying metabolic dysregulation, and hormonal ratios, especially the leptin/adiponectin ratio, are more accurate indicators of this imbalance than individual hormone measurements.