Apolipoproteins E (APOE) and A1 (APOA1) are key regulators of lipid metabolism and have been individually associated with dyslipidemia and type 2 diabetes mellitus (T2DM).<h4>Objective</h4>This study aimed to examine the individual and combined associations of APOE (rs429358, rs7412) and APOA1 (rs5069) gene polymorphisms with obesity and T2DM.<h4>Methods</h4>A case-control study was conducted including 350 participants categorized into four groups: controls (n = 100), euglycemic obese individuals (n = 100), obese individuals with T2DM (n = 100), and non-obese individuals with T2DM (n = 50). The gene discussed is APOE; the disease is obesity due to melanocortin 4 receptor deficiency.