Diabetes mellitus (DM) is a persistent and steadily progressing metabolic condition distinguished by unregulated high levels of blood glucose. GLP1 receptor agonists have recently gained recognition as first-line therapies in selected instances, as per the updated ADA guidelines, highlighting their efficacy not only in glycemic control but also in their broader health benefits. Nonetheless, the efficacy of GLP-1 is limited by its brief duration of action, rapid clearance from the body, and challenges associated with subcutaneous administration. In this study, we examined the potential diabetes-mitigating effects of a genetically engineered strain of Escherichia coli Nissle 1917 (EcN)-GLP-1, previously developed by our group. We utilized mouse models for both Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM) to assess its efficacy. In the case of T1DM mice, the results revealed that EcN-GLP-1 resulted in a notable decrease in blood glucose levels. Furthermore, it exhibited a protective influence on the structural integrity of islet