Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 02 11 1 8 EN Amir Pedram Moghis Department of Medicine, Faculty of Medicine, Hamadan University Medical Sciences, Hamadan, Iran Mehdi Behzad Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran Alireza Soltanian Modeling of Noncommunicable Diseases Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Shiva Borzouei Department of Endocrinology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran 2025 05 26 2025 10 20 Type 2 diabetes (T2D) is defined by persistent inflammatory processes. This study evaluated the anti-inflammatory properties of empagliflozin in combination with metformin therapy in patients with T2D. In this prospective cohort study, 50 individuals with type 2 diabetes were non-randomly assigned to receive metformin (MTF, n = 25) or empagliflozin (10 mg/day) and metformin (EMPA+MTF, n = 25) and followed for 6 months. Fasting blood glucose (FPG), HbA1c, body mass index (BMI), glomerular filtration rate (GFR), and urinary albumin were measured at baseline and then 6 months later. Interleukin-1beta (IL-1β) and interleukin-6 (IL-6) secretion from isolated and stimulated peripheral blood mononuclear cells were measured using ELISA and compared in the different study groups. The MTF+EMPA group showed significantly decreased levels of FPG, HbA1C, and body mass index compared to the baseline. FPG and HbA1c in the MTF+EMPA group showed a significant decrease six months after treatment versus the MTF group. A significant reduction in IL-1β levels was observed at the six months post-treatment compared to baseline and in relation to the MTF group after six months. The levels of IL-6 exhibited no significant differences, both within and between the study groups. Significant direct correlations were observed between IL-1β levels and FPG as well as HbA1c within the MTF+EMPA group following six months of treatment. Incorporating empagliflozin (10 mg/day) into metformin treatment markedly enhanced glycemic regulation and lowered IL-1β secretions, indicating a possible anti-inflammatory benefit in overweight individuals with T2D following six months of treatment. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4466 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4466/2305