Available data comparing the efficacy of liraglutide and semaglutide in managing weight loss is limited. The objective of this study was to compare efficacy of both drugs on weight loss.A retrospective observational cohort study conducted at our quaternary care hospital from June 2018 to July 2022. The study included adults who received either liraglutide or semaglutide during the study period. The primary outcome was weight loss, while secondary outcomes included effects on HbA1c levels and lipid profile.A total of 366 patients were analyzed (122 on liraglutide, 244 on semaglutide). The groups were comparable in mean age (51.00 ± 11.55 vs 51.16 ± 12.35 years, = 0.521) and baseline mean weight (94.7 ± 19.5 vs 94.6 ± 19.9 kg, = 0.989). After a median follow-up of 10 (6-17) months for the liraglutide group and 7.5 (6-11) months for the semaglutide group ( < 0.001), the resultant weights were 90.8 ± 19.6 kg for the liraglutide group and 91.1 ± 19.8 kg for the semaglutide group ( < 0.001) when comparing each group to its baseline separately. When comparing the weight loss achieved in each group, liraglutide achieved a median weight loss of -4 (-7 to 0) kg versus -3 (-6 to 0) kg for semaglutide ( = 0.867). The reduction in HbA1c levels with liraglutide was significantly less than with semaglutide: -0.2 (-0.5 to 0.3) versus -0.5 (-1.1 to 0.1), respectively, ( = 0.003). Both drugs significantly lowered LDL and triglycerides. Multivariable linear regression analysis confirmed no significant difference between the drugs [-0.577, 95% CI -1.87 to 0.7; = 0.38], while baseline weight, diabetes, and SGLT2 inhibitors were significant factors affecting weight.Both liraglutide and semaglutide were effective in reducing weight, with no significant difference between the two drugs. However, semaglutide was more effective in reducing HbA1c levels.