Obesity and Type 2 Diabetes Mellitus (T2D) are influencing aging population. Weight management is extremely important for older adults, but currently trials elucidating the effective and safe treatment for weight reduction in older adults with T2D are scarce. Aim of this study was compare the action of GLP-1 receptor agonists (GLP1-RAs) and sodium glucose co-transporters inhibitors (SGLTis) on body weight (BW) loss and HbA1c improvement in older patients (aged ≥70) with overweight/obesity (BMI ≥27 kg/m2) and T2D. Patients treated with DPP-4is were considered as control. 23 patients (8 F/15 M) treated with SGLT2is, 38 patients (11 F/27 M) treated with GLP-RAs and 15 patients (11 F/4 M) treated with DPP-4is were considered. Data were analyzed at baseline (T0=start of treatment) and after 6 (T1) and 12 (T2) months. At T2, no significant difference was found in ΔBMI between SGTL2is (-1.67±0.22 kg/m2) and GLP1-RAs groups (-1.34±0.28 kg/m2). As expected, BMI variation in DPP-4is group (-0.27±0.29 kg/m2) was significantly lower compared to two groups (p≤ 0.05). GLP1-RAs revealed more efficacious than both DPP-4is (p=0.0003) and SGTL2is (p=0.021) in significantly reducing HbA1c. In GLP1-RA group, unlike dulaglutide, semaglutide was more effective in promoting BW loss compared to DPP-4is (p=0.046). By analyzing the data according to the sex, in the female subgroup the effective of GLP1-RAs and SLGT2i was limited and no significant differences between the 3 treatments emerged. Furthermore, in male and female subgroups of GLP1-RAs, HbA1c decrease tended to be more significant than in the DPP-4is subgroups (respectively, p=0.057 and p=0.063). Collectively, our data indicate that GLP1-RAs and SGLT2 inhibitors represent a valid and tailored therapeutic option in elderly patients with T2D associated overweight/obesity, above all for male subjects. Even if further research is needed, our study suggests that a precision medicine approach is fundamental to improve the weight management in older adults with T2D.