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Objective: Exenatide (twice daily) has been used as a glucagon-like peptide-1 receptor agonist in patients with diabetes with inadequate glycemic control for over a decade. In this paper, we aimed to investigate the long-term glycemic control and change in body weight in patients treated with exenatide. Methods: A total of 287 patients who were treated with exenatide twice daily between 2012 and 2022 were included in this retrospective study. The changes in glycated hemoglobin (HbA1c) levels and body weight were assessed over time after exenatide administration. The administered insulin dosage and metabolic parameters were documented. The baseline data were compared over a period of 3 months to 3 years. Results: The study included 101 (36%) males and 186 (64%) females, with an average age of 56.4 ± 10.7 years. The baseline HbA1c level was 8.0 ± 1.8%, and the body mass index was 38.8 ± 5.9 kg/m². The HbA1c level had decreased by 1.29% from the baseline at 3 months (P < .001), which continued up to 3 years (−0.63%, P = .010). During the 3-year period, body weight continued to decrease significantly (−12.1, P < .001). Glucose levels were significantly reduced, but the lipid levels and glomerular filtration rate after exenatide treatment were similar. Notably, exenatide administration resulted in a decrease in insulin dosage for patients treated with insulin. Conclusion: Exenatide therapy produced continued improvements in glycemic control and progressive weight loss for 3 years in patients with diabetes in a real-life setting. [ABSTRACT FROM AUTHOR]