METFORMIN-BASED COMBINATION THERAPY DIFFERENTIALLY MODULATES ADIPONECTIN AND LIPID PROFILE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Abstract

Objectives: This study aimed to evaluate the effects of different metformin-based combination therapies on circulating adiponectin levels and lipid profile parameters in patients with type 2 diabetes mellitus (T2DM) and to compare the metabolic responses associated with each therapeutic regimen. Methods: A prospective observational analysis was performed involving 70 patients diagnosed with T2DM who were undergoing metformin-based treatment at a tertiary-level healthcare facility. Participants were categorized into three treatment groups: Metformin+sulfonylurea (n=24), metformin+dipeptidyl peptidase-4 (DPP-4) inhibitor (n=23), and metformin+sodium-glucose cotransporter-2 (SGLT-2) inhibitor (n=23). Baseline and follow-up evaluations comprised fasting blood glucose, glycated hemoglobin (HbA1c), lipid parameters including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides, along with serum adiponectin concentrations determined by Enzyme-Linked Immunosorbent Assay during a 6-month follow-up period. Results: Baseline demographic, glycemic, and biochemical characteristics were generally comparable, although HDL-C differed modestly among the groups (p=0.04). HbA1c decreased by 0.71±0.38%, 0.95±0.34%, and 1.83±0.42% in the sulfonylurea, DPP-4 inhibitor, and SGLT2 inhibitor groups, respectively. The corresponding reductions in TC were 5.86±8.62, 12.01±8.34, and 33.59±10.27 mg/dL, whereas LDL-C declined by 2.95±5.48, 10.46±6.15, and 25.12±7.38 mg/dL. Triglyceride reductions were also greatest with the SGLT2 inhibitor combination. Adiponectin increased by 0.13±0.32, 0.85±0.38, and 2.22±0.46 μg/mL across the three groups. Overall differences in the measured treatment-related changes were statistically significant (all p<0.01). Conclusion: Metformin-based combinations were associated with differing metabolic responses. The SGLT2 inhibitor combination showed the largest improvements in glycemic control, atherogenic lipid parameters, and circulating adiponectin, whereas the DPP-4 inhibitor combination produced intermediate changes. These findings support further evaluation of SGLT2 inhibitor-based therapy as a strategy for broader cardiometabolic risk management in type 2 diabetes.