Marta Owczarzak, Agnieszka Siwiec, Maria Morawska, Diana Szczepańska, Aleksander Ruszkiewicz, Alicja Ożga, Anna Dargacz, Daria Drężek, Julia Kozikowska, Klaudia Szymczyk, Maciej Jakubik, Marta Kiżewska, Aleksandra Gajos, Zuzanna Wójcik, Michalina Raczkowska
Research objective: The aim of this study is to review the available literature and compare the gastrointestinal adverse effects of selected anti-obesity medications — orlistat, bupropion/naltrexone, liraglutide, semaglutide, and tirzepatide — in the context of the worldwide increase in obesity prevalence and the growing popularity of these drugs, particularly GLP-1 agonists. Methodology: The study is based on a review of the available literature concerning the type and reported frequency of gastrointestinal adverse effects of older and newer anti-obesity medications, with particular attention to dose dependence, the time course of symptoms during treatment, and the reasons for treatment withdrawal. Main conclusions: The most common adverse effects of orlistat are fatty diarrhea (20% of patients treated with 120 mg daily) and fecal urgency (22% at the same dose). Bupropion with naltrexone causes the mildest adverse effects among the drugs reviewed, most commonly nausea, reported in 33% of patients. Among the GLP-1 agonists, gastrointestinal adverse effects were reported most frequently by patients treated with semaglutide; for each agonist, nausea and vomiting predominated and were the primary reasons for treatment withdrawal. Adverse effects were dose-dependent and tended to resolve naturally over the course of treatment, and tirzepatide showed the best efficacy-to-adverse-effects ratio. Application of the study: The distinct differences in the type and frequency of gastrointestinal adverse effects between the analyzed drugs may support clinicians in selecting the most appropriate treatment option for each individual patient. Originality/Novelty of the study: The review directly compares older and newer generations of anti-obesity medications, addressing the question of whether the increasingly popular GLP-1 agonists carry a greater burden of gastrointestinal adverse effects than earlier agents, and positions tirzepatide in terms of its efficacy-to-tolerability balance.