Background: Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated superior efficacy for weight management, leading to its rapid uptake since approval. However, reports of adverse events (AEs) have raised safety concerns among users. While clinical trials have documented AE profiles, real-world evidence on users\' knowledge, attitudes, and practices (KAP) regarding semaglutide and their association with AE occurrence remains limited.

Objectives: To evaluate the KAP of semaglutide users in South Korea and identify factors associated with AE occurrence.

Methods: This cross-sectional survey was conducted between September and October 2025, approximately one year after the launch of semaglutide (Wegovy ®) in South Korea. Adults who had been prescribed semaglutide for weight loss within the past year were recruited through online communities using quota sampling stratified by sex, age, and region (N=498). Knowledge, attitudes, and practices regarding semaglutide use were assessed using a structured questionnaire; descriptive results were summarized as proportions (%), and analytic variables were constructed as composite scores reflecting correct knowledge, positive attitudes, and appropriate or inappropriate practices. Participants reported any AEs experienced during treatment. Multivariable logistic regression models were used to identify factors associated with AE occurrence; results are presented as odds ratios (OR) and 95% confidence intervals (CI).

Results: Among 498 participants, 306 (61.4%) experienced at least one AE. Participants showed high levels of knowledge of administration (90.2%) and mechanism of action (89.4%) and had positive attitudes towards safety (82.3%) and efficacy (88.4%). However, despite high knowledge and favorable attitudes, unsafe practices were reported, including dosage splitting (55.8%) and sharing pens (10.4%). In multivariable logistic regression analyses, AE occurrence showed was significantly associated with reliance on sources other than healthcare professionals or official product labeling (OR 2.14, 95% CI 1.35 – 3.41), adjusting for demographic characteristics.

Conclusions: Semaglutide users showed high levels of knowledge and positive attitudes, but AE occurrence was associated with non-professional information sources rather than overall knowledge or attitudes. These findings highlight a behavioral dimension of pharmacovigilance, suggesting that risk minimization strategies should address information ecology and real-world usage behaviors beyond knowledge alone.