(A-081) Effect of Orlistat on Bodyweight Among Adults With Overweight or Obesity Without Diabetes: Emulation of a Target Trial Using UK Electronic Medical Records

Background: Obesity poses a public health challenge globally, increasing risks of chronic conditions, including cardiovascular disease, and all-cause mortality. Pharmacological options for weight management are limited, with orlistat being the only oral anti-obesity therapy recommended by UK guidelines and advised for individuals with BMI ≥30 kg/m2 or ≥28 kg/m2 with comorbidities, while injectable agents (e.g., semaglutide) are typically reserved for BMI ≥35 kg/m2. Although clinical trials have demonstrated the efficacy of orlistat for weight management, the real-world effectiveness across different body-mass index (BMI) categories is lacking.

Objectives: To assess the real-world effectiveness of orlistat on bodyweight outcomes in UK primary care, stratified by BMI categories.

Methods: Using the IQVIA Medical Research Data (IMRD) incorporating data from THIN, A Cegedim Database, we conducted a cohort study of adults with a BMI measurement ≥25 kg/m2 recorded between 01-Jan-2006 and 30-Jun-2023. Following a target trial framework, orlistat initiators were propensity-score matched (1:4) to non-initiators eligible to start orlistat at the same time. Co-primary outcomes were percentage change in bodyweight and achievement of ≥5% weight loss at 6-months, evaluated by intention-to-treat analyses using ANCOVA and logistic regression, respectively. Additionally, we stratified the ≥5% weight loss outcome by BMI category: overweight (25.0-29.9 kg/m2), obesity class 1 (30.0-34.9 kg/m2), obesity class 2 (35.0-39.9 kg/m2), and obesity class 3 (≥40 kg/m2).

Results: We included 82,530 individuals who initiated orlistat (mean age: 43.5 years, 79.5% female), distributed across BMI categories: overweight (7.9%), obesity class 1 (36.4%), obesity class 2 (33.4%), and obesity class 3 (22.3%), and matched to 330,106 non-initiators. At 6-months, bodyweight change was greater among orlistat initiators (-3.56%, SE 0.1) compared non-initiators (-1.19%, SE 0.1; estimated treatment difference: -2.30%; 95% CI -2.38, -2.22). Orlistat initiators were more likely to achieve ≥5% weight loss than non-initiators (37.1% vs 21.0%; odds ratio [OR] 2.20, 95% CI 2.14-2.26). Proportions of orlistat initiators achieving ≥5% weight loss by BMI category were: overweight 30.5% (OR 2.13; 95% CI 1.91-2.38); obesity class 1 36.2% (OR 2.44; 95% CI 2.33-2.56); obesity class 2 37.3% (OR 2.19; 95% CI 2.09-2.30), and obesity class 3 40.5% (OR 1.91; 95% CI 1.80-2.03).

Conclusions: Orlistat initiation was associated with significantly greater weight loss across all BMI categories. Our findings support orlistat as an effective pharmacological option for weight management across UK primary care, particularly for those with overweight or moderate obesity who may not qualify for injectable agents.