Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has emerged as a favourable treatment option for patients with obesity and type 2 diabetes mellitus (T2DM). The growing demand, rapid uptake, regional variations in prescribing, safety concerns, socioeconomic inequalities, off-label use, and supply challenges demand regular policy review and the need to evaluate regional prescribing patterns, safety profiles, and socioeconomic determinants of semaglutide in England. The study examined prescribing trends, adverse drug reactions (ADRs) and socioeconomic influences associated with semaglutide, liraglutide, orlistat and tirzepatide across various regions of England between 2020 and 2024.Given its increasing use and demonstrated efficacy in clinical trials, semaglutide was the focus of a detailed evaluation of prescribing patterns and associated ADRs. The study also examined liraglutide and tirzepatide, comparing them with the long-established anti-obesity drug orlistat. This study aims to provide clinicians and policymakers with key insights into prescribing trends, safety concerns, and regional disparities, thereby supporting informed clinical decision-making in the treatment of obesity and T2DM.This retrospective observational study utilised NHS Open Data prescribing (English dataset) from 2020 to 2024 and Medicines and Healthcare products Regulatory Agency (MHRA) Yellow Card ADR reports. Prescribing rates (items per 100,000 population), cost metrics and formulation-specific trends were analysed across English regions. Socioeconomic factors were examined using the Index of Multiple Deprivation (IMD), the prevalence of overweight individuals, and the percentages of minority ethnic populations. Statistical analyses included linear regression and generalised additive models using R and SPSS version 26.Prescriptions for semaglutide and tirzepatide increased significantly, while orlistat prescribing remained stable, and liraglutide use declined during the study period. Semaglutide prescribing rose nationally from 469.39 items per 100,000 population in 2020 to 2668.20 in 2024. The highest rates were observed in the North West (3,624.04 per 100,000) and the North East & Yorkshire (3,412.89), with the Midlands showing the most significant growth in 2024. Oral formulations of semaglutide (Rybelsus®) exhibited substantial uptake, rising from 1.59 to 1448.42 items per 100,000. Cost metrics shifted over time: London consistently recorded the highest cost per item, while most regions showed reductions. The cost per quantity decreased from £67.94 in 2020 to £4.84 in 2024, indicating improved cost-efficiency. Socioeconomic analysis revealed a positive correlation between minority ethnic proportion and annual prescribing growth, as well as a weak negative association with deprived levels.ADR reports increased from 144 to 2,780 in 2024, primarily driven by gastrointestinal disorders. Case fatality rates were highest for cardiac disorders (9.2%) and endocrine neoplasms (20%). Between 2020 and 2024, the prescribing of semaglutide in England increased substantially, accompanied by regional disparities and cost reductions. The rise in prescriptions was paralleled by an increase in ADR reports, underscoring the importance of ongoing pharmacovigilance. Minority ethnic representation emerged as a significant socioeconomic factor influencing the growth of prescription medication use. Regional and demographic variations suggest that prescribing is shaped by factors beyond clinical need, highlighting the persistence of healthcare inequalities. These findings provide actionable insights for prescribing policy, draw attention to emerging safety concerns and identify priorities for future research, particularly regarding equitable access and the long-term outcomes of anti-obesity and anti-diabetic therapies. Sustained efforts are required to ensure prescribing practices remain safe, efficient, and equitable.