Type 2 Diabetes (T2D) is associated with greater difficulty in losing body weight (BW) in people with obesity. Hyperglycaemia alters several neuronal mechanisms related to eating behaviour and reward circuit. Recent data have showed that GLP-1 receptor agonists (GLP-1RAs) and also SGLT2 inhibitors (SGLT2is) influence the brain functions related to appetite control. Similarly, our research group have demonstrated the efficacy of 5-week treatment with high frequency repetitive Transcranial Magnetic Stimulation (rTMS) on control food craving and reduction of BW up to 1 year period in individuals with obesity. Aim of this study was to compare the efficacy of GLP1-RAs, SGLT2is, and rTMS in reducing BW up to 1 year in patients with obesity and T2D/IFG, by investigating possible sex-related differences. For a retrospective comparative analysis 40 patients (21F/19M) treated with SGLT2is, 37 patients (22F/15M) treated with GLP1-RA, 30 patients (20F/10M) treated with rTMS were considered and BMI were evaluated at baseline (T0), after 6 months (T1) and 1 year (T2). At T2 compared to T0, a significant BW reduction was detected in each of the three intervention groups, even if the SGLT2is-BMI trend appeared dissimilar compared to the other 2 groups, by re-increasing after T1. The analysis of BMI based on sex difference revealed that in SGLT2is-females there was a significant BMI increase T1-T2 (SGLT2is vs GLP1-RA, p=0.03; SGLT2is vs rTMS, p=0.05). Moreover, in the SGLT2is group, males BW changes are significantly higher compared to females after T1 (ΔBMI: females -0.06±0.27 vs males -1.34±0.34, p=0.01). A trend towards greater BW loss was observed in females compared to males within the GLP1-RA group (ΔBMI: females -2.68±0.49 vs males -1.34±0.45, p=0.07). For the first time, we demonstrated that rTMS is comparable to SGLT2is and GLP1-RAs in promoting BW loss in patients with obesity and T2D/IFG. Significant gender differences emerged in the response to the 3 treatments: a better female response to GLP1-RAs on the contrary a worse response in women treated with SGLT2is, especially after 6 months, and, no difference was observed in rTMS group.