Objectives: Exenatide, a glucagon-like peptide 1 (GLP-1) receptor agonist, reduces glycated hemoglobin (A1C) and body weight (BW) and improves cardiovascular (CV) risk factors in some but not all patients. This study was planned to evaluate a potential gender difference of exenatide\u2019s effects in diabetic subjects. Study Design: A retrospective study comparing metabolic control and changes in weight, waist circumference, and body mass index according to gender. Methods: We retrospectively collected clinical data from 69 outpatients with type 2 diabetes mellitus (34 male and 35 female), mean age = 52.6 years (SD = 10.3); mean duration of diabetes = 9.4 years (SD = 5.4) with persistent exenatide treatment, evaluating the evolution of anthropometric, clinical, and metabolic parameters. Results: Exenatide rapidly reduced A1C, fasting plasma glucose (FPG), BW, and waist circumference (WC) in both genders (all P values <.0001). WC was more reduced in women after 12 months of treatment (P =.02). After 24 months, patients showed a stable reduction of A1C and FPG (all P values <.0001 vs baseline) without any gender-related difference, while BW lowering was more pronounced in women compared with men (P =.002). Conclusions: Exenatide effected a sustained improvement in metabolic and anthropometric parameters in both genders, but BW and WC were more reduced in females. The women with diabetes experienced a more prominent therapeutic benefit for some CV risk factors and a reduction in waist circumference and body weight