Disorders linked to increased body weight are on the rise and obesity is a global epidemic associated with a rising risk for developing comorbidities, such as hypertension or type 2 diabetes. There is a significant need to develop a multimodal approach targeting obesity within clinical medicine. Pharmacological options to produce weight loss have been a popular research area and the novel glucagon-like Peptide-1 receptor agonists (GLP-1 RA) are highly effective glycemic control agents that have shown a substantial weight loss effect. This systematic review explores the efficacy of semaglutide, a GLP-1 RA agent, in a non-diabetic population, looking at endpoints of changes in weight and waist circumference and the percentage of patients achieving a clinically effective weight loss of at least 5%. This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive search was undertaken to find applicable papers using three databases, including PubMed, PubMed Central, and Cochrane Library. The included articles were narrowed down from an initial pool of 423 papers using filters, automation tools, inclusion/exclusion criteria, and quality appraisal tools. In this systematic review, we have analyzed 10 high-quality studies published in the last five years, including nine randomized control trials (RCTs) and a retrospective cohort study. The aim was to combine the results of these studies, encompassing 6623 participants, to showcase the effectiveness of GLP-1 RAs in the non-diabetic obese or overweight population. The consolidated data from the literature in this systematic review endorses the use of semaglutide as a highly efficient weight-reducing agent, contributing positive insight to both clinicians and researchers in the field of obesity treatment.