The combined effects of glycemic dysregulation, dyslipidemia, and cellular stress responses lead to increased expression of glucose-regulated protein-78 (GRP-78), a key mediator in type 2 diabetes mellitus (T2DM) development. Due to its involvement in glucose and lipid metabolism, GRP-78 is considered a potential therapeutic biomarker. This study aimed to assess the impact of various antidiabetic medications on GRP-78 levels in individuals with T2DM. A cross-sectional study comprised 134 participants: 96 T2DM patients who were divided into patients under treatment with glucovance 500 (n=38), or insulin injection (n=42), and newly diagnosed diabetic patients (n=16). A control group of 38 healthy subjects were enrolled. Serum levels GRP-78 were measured using the ELISA method and lipid profiles were measured by standard biochemical tests. HbA1c levels in blood were determined using the Roche Cobas c111 analyzer. Statistical analyses were performed using ANOVA and Pearson correlation. In patient groups, GRP-78 levels were significantly higher than healthy controls (p<0.05). Patients with insulin treatment had the highest GRP-78, followed by patients with glucovance 500 and newly diagnosed. Both patient groups under treatment demonstrated a strong positive link between HbA1c and GRP-78, whereas newly diagnosed groups showed a medium correlation. The insulin group had reduced triglycerides and increased HDL levels. Higher GRP-78 levels in T2DM patients support glycemic control and endoplasmic reticulum stress. GRP-78 may be a glycemic biomarker due to its significant connection with HbA1c. Different lipid profiles show how therapy affects metabolic parameters. The research focused on the GRP-78's role in T2DM management and treatment.
