Purpose This study aimed to conduct a comprehensive drug use evaluation (DUE) of injectable glucagon-like peptide-1 receptor agonists (GLP-1RAs) within Singapore’s largest healthcare cluster, focusing on the appropriateness of indication, efficacy in weight loss and glycemic control, and safety profile. Method A retrospective review of medical records was conducted for patients prescribed injectable GLP-1RAs (dulaglutide, liraglutide, or semaglutide) between July 2022 and June 2023 across SingHealth institutions. Appropriateness of indication was assessed against approved criteria. Efficacy was evaluated by changes in HbA1c for type 2 diabetes mellitus (T2DM) patients and body weight for those receiving treatment for weight loss. Safety was assessed by reviewing documented adverse events. Logistic regression analyses identified predictors of efficacy and safety. Results Among 915 patients included, the majority were female (53.3%), aged 35–64 years (74.4%), and had obesity (80%). Appropriate prescribing rates were 96.3%, primarily for weight loss (65.2%) and T2DM (31.0%). Efficacy analysis showed 51.3% of patients achieved ≥5% weight reduction, while 58.7% attained ≥1.0% HbA1c reduction. Adverse events were reported in 37.9% of patients, predominantly gastrointestinal symptoms. Factors influencing outcomes included treatment duration, GLP-1RA type, and baseline clinical parameters. Conclusion The DUE affirmed the appropriateness, efficacy, and safety of injectable GLP-1RAs for weight loss and T2DM management in a real-world setting. The findings provide actionable insights to optimise GLP-1RA utilisation and improve patient outcomes, emphasising the importance of patient selection, monitoring, and education in maximising therapeutic benefits.