Obesity is a chronic, complex disease linked to major illness and death. Related conditions include heart disease, type 2 diabetes, and cancer. Its global prevalence has soared, demonstrating the need for treatments beyond lifestyle change. Pharmacotherapy is essential, particularly for people unable to maintain weight loss through behavioural interventions. This review evaluates the efficacy and safety of glucagon-like peptide-1 (GLP-1) receptor agonists, specifically semaglutide and liraglutide. These are assessed against established anti-obesity drugs, including orlistat and phentermine. A structured search was carried out across PubMed, Scopus, and Google Scholar. Priority was given to randomised controlled trials, meta-analyses, and large observational studies published from 2010 to 2025. Key clinical trial programmes, such as STEP, SUSTAIN, LEADER, SELECT, and SURMOUNT, were critically reviewed. Semaglutide shows superior efficacy. Mean weight reductions often exceed 10–15%. These reductions are linked to considerable improvements in glycaemic and cardiometabolic parameters. Liraglutide provides modest weight loss but has proven cardiovascular benefits. Orlistat and phentermine have lower efficacy. They also have tolerability issues and limited long-term use. Despite their strengths, GLP-1 receptor agonists cause gastrointestinal side effects, high cost, and have limited long-term safety data. GLP-1 receptor agonists represent a major advance, making obesity treatment more targeted. Future studies ought to focus on long-term outcomes, accessibility, and improving the tolerability and affordability of therapy.
Handzel et al. (Wed,) studied this question.