Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly prescribed medications for patients with type 2 diabetes mellitus (T2DM) based on cardiovascular benefits. Objective This study aimed to evaluate efficacy and tolerability of once daily liraglutide vs once weekly semaglutide on T2DM in a Veteran population. Methods This was a retrospective, single-center, cohort study that included T2DM patients with a prescription for liraglutide or semaglutide between September 1st, 2019, and September 30th, 2020. Patients between groups were matched based on age and insulin use at baseline. The primary endpoint was the difference in hemoglobin A1c (A1c) between the most recent A1c in the study period and baseline A1c obtained prior to GLP-1 RA initiation. Results There were 154 patients included in the study. While mean reduction in A1c was numerically higher in the liraglutide group (−1.1% vs. −.8%), this was not statistically significant ( P = .22). The proportion of patients achieving A1c < 7%, < 8%, < 9%, or their patient-specific A1c goal did not differ between groups. Although baseline total daily doses of insulin were higher in the semaglutide group, these patients had numerically greater reductions in total daily dose of insulin and weight from baseline; however, no statistical difference was observed. Adverse drug reactions were more common in the semaglutide group (n = 14 vs. 9), leading to higher discontinuation rates as well (n = 11 vs. 8). Conclusion The results of this study indicate no difference between liraglutide and semaglutide in terms of A1c-lowering potential, but it provides insights into key considerations for the Veteran population.