Background: SGLT2 inhibitors (SGLT-2i) and GLP1 receptor agonists (GLP-1 RA) are recommended as the first line therapy for the management of type 2 diabetes mellitus (T2DM), particularly in patients with chronic kidney disease (CKD), cardiovascular disease (CVD), and heart failure (HF). Despite their established efficacy, there is limited evidence available to predict which subset of patients will respond favorably to them. We conducted this study to identify baseline characteristics to predict the response to therapy with SGLT-2i and GLP-1 RA. Methods: A retrospective analysis of the medical records was conducted at the Veteran Affairs Medical Center (VAMC) in Omaha, Nebraska, USA. Veterans who had completed 6–12 months of treatment with SGLT-2i or GLP-1 RA were included. Favorable treatment outcomes were a ≥0.5% reduction in glycosylated hemoglobin (HbA1c) or a ≥5% reduction in body weight; and those who achieved both outcomes were classified as adequate responders. Results: Patients in the GLP-1 RA group had 2.11 (95% CI: 1.45, 3.07) times the odds of achieving an adequate response as compared to patients in the SGLT-2i group in the unadjusted analysis, p < 0.001. HbA1c > 8% and older age was significantly associated with achieving an adequate response. Conclusions: Treatment with GLP-1 RA should be considered in Veterans with these characteristics.