Comparative effectiveness of long-term anti-obesity medications in routine clinical practice: a retrospective cohort study using real-world data

Orlistat, phentermine/topiramate, and liraglutide are widely used obesity pharmacotherapies, but comparative data from Asian real-world settings remain limited.We compared their effects on body weight, glycemic control, and persistence.We performed a retrospective cohort study using electronic health records from a tertiary hospital in Korea.Adults prescribed orlistat, phentermine/topiramate, or liraglutide between 2018 and 2025 were included.The primary endpoint was percentage weight change at 6 months.Secondary endpoints were the proportions achieving ≥5% and ≥10% weight loss, weight change at 3, 6, and 12 months, change in HbA1c, and 12-month treatment persistence.We applied multivariable linear and logistic regression, linear mixed-effects models, propensity score-weighted models, and Kaplan-Meier and restricted mean survival time (RMST) methods.Among 1,910 treatment episodes, 505 involved orlistat, 777 phentermine/topiramate, and 628 liraglutide.Phentermine/ topiramate showed greater mean percentage weight loss at 6 months than orlistat (adjusted difference, -1.59 percentage points; p < 0.001), whereas liraglutide produced similar weight loss to orlistat.The odds of achieving ≥5% weight loss were higher with phentermine/topiramate than with orlistat (adjusted odds ratio, 2.21), while liraglutide showed a smaller effect.Liraglutide tended to reduce HbA1c more than orlistat, but this difference was attenuated after propensity score weighting.Twelve-month treatment persistence and RMST were lower with liraglutide than with the oral agents.In this real-world cohort, phentermine/topiramate achieved the most pronounced and sustained weight loss.Liraglutide and orlistat produced similar overall weight reduction, but liraglutide showed lower long-term persistence.