Multifactor Quality and Safety Analysis of Semaglutide Products Sold by Online Sellers Without a Prescription:Market Surveillance,Content Analysis, and Product Purchase Evaluation Study

Background: Over the past 4 decades, obesity has escalated into a global epidemic, with its worldwide prevalence nearlytripling. Pharmacological treatments have evolved with the recent development of glucagon-like peptide 1 agonists, such assemaglutide. However, off-label use of drugs such as Ozempic for cosmetic weight loss has surged in popularity, raising concernsabout potential misuse and the emergence of substandard and falsified products in the unregulated supply chain.Objective: This study aims to conduct a multifactor investigation of product quality and patient safety risks associated with theunregulated online sale of semaglutide by examining product availability and vendor characteristics and assessing product qualitythrough test purchases.Methods: We used a complex risk and quality assessment methodology combining online market surveillance, search engineresults page analysis, website content assessment, domain traffic analytics, conducting targeted product test purchases, visualquality inspection of product packaging, microbiological sterility and endotoxin contamination evaluation, and quantitative sampleanalysis using liquid chromatography coupled with mass spectrometry.Results: We collected and evaluated 1080 links from search engine results pages and identified 317 (29.35%) links belongingto online pharmacies, of which 183 (57.7%) led to legal pharmacies and 134 (42.3%) directed users to 59 unique illegal onlinepharmacy websites.Web traffic data for the period between July and September 2023 revealed that the top 30 domains directlyor indirectly affiliated with illegal online pharmacies accumulated over 4.7 million visits.Test purchases were completed from6illegal online pharmacies with the highest number of links offering semaglutide products for sale without prescription at thelowest price range. Three injection vial purchases were delivered; none of the 3 Ozempic prefilled injection pens were receiveddue to nondelivery e-commerce scams.All purchased vials were considered probable substandard and falsified products, as visualinspection indicated noncompliance in more than half (59%-63%) of the evaluated criteria. The semaglutide content of samplessubstantially exceeded labeled amounts by 28.56%-38.69%, although no peptide-like impurities were identified. The lyophilizedpeptide samples were devoid of viable microorganisms at the time of testing; however, endotoxin was detected in all samples with levels ranging between 2.1645 EU/mg and 8.9511 EU/mg. Furthermore, the measured semaglutide purity was significantlylow, ranging between 7.7% and 14.37% and deviating from the 99% claimed on product labels by manufacturers.Conclusions: Glucagon-like peptide 1 agonist drugs promoted for weight loss, similar to erectile dysfunction medications morethan 2 decades ago, are becoming the new blockbuster lifestyle medications for the illegal online pharmacy market. Protectingthe pharmaceutical supply chain from substandard and falsified weight loss products and raising awareness regarding onlinemedication safety must be a public health priority for regulators and technology platforms alike