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Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonists (GLP-1/GIP RAs) effectively manage type 2 diabetes mellitus (T2DM). Recent medication shortages have impacted patient access to treatment. The objectives of this study were to evaluate the effect of incretin therapy shortages on glycemic control and adverse patient outcomes. This retrospective cohort study evaluated the impact of interruptions in therapy on patients receiving maintenance doses of incretin therapy for at least three months. Patients were excluded if they were not on adequate maintenance doses, had missing hemoglobin A1c (HbA1c) levels, discontinued therapy due to side effects or cost, or had a history of chronic glucocorticoid use or organ transplant. The primary outcome was HbA1c levels before and after therapy interruption. Secondary outcomes were the incidence of gastrointestinal issues, hyperglycemia, and hypoglycemia-related hospital/clinic visits. A total of 71 patients were included. The median therapy duration was 9 months. Patients had a baseline HbA1c of 6.9%. Following interruption, 25.4% of patients had glucose-lowering therapy additions to their regimen, 35.2% dosage adjustments, and 39.4% no changes. HbA1c increased significantly to 7.2% at 12 months (P < 0.001). No significant differences were observed in adverse events or clinic/hospital visits (P = 0.571 and P = 1.00). Shortages of incretin therapy significantly increased patients' HbA1c levels up to 12 months post interruption. Long-term shortages or restrictions of these agents are likely to lead to adverse clinical outcomes. Further studies are needed to assess the outcomes of prolonged shortages or restrictions of these therapies.