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Key points: Semaglutide and orlistat have different mechanisms of action for weight loss: semaglutide slows digestion by mimicking GLP-1 (a fullness hormone), while orlistat reduces fat absorption in the gut No published evidence exists on combining these drugs, making outcomes and potential interactions uncertain, though healthcare professionals may recommend combination use to kickstart weight loss Both medications can cause gastrointestinal side effects: semaglutide may lead to nausea, constipation, and vomiting, while orlistat can cause oily stools and diarrhoea While side effects are generally mild and transient, combined use may increase susceptibility to these effects, potentially impacting quality of life The interaction between semaglutide and orlistat when used together is unclear, particularly regarding how semaglutide might affect orlistats action in the gut due to a lack of research on their combination 2) Weight loss with semaglutide and orlistat Research has shown that semaglutide supports an average weight loss of around 15% after one year on the medication