Nonadherence to GLP‐1 Receptor Agonists Among Individuals With Overweight or Obesity: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Background Glucagon‐like peptide 1 (GLP‐1) agonists are widely used for obesity management in patients with or without diabetes. However, treatment persistence is often limited due to adverse drug reactions (ADRs). Understanding adherence patterns in randomized controlled trials (RCTs) is crucial for predicting real‐world treatment acceptance. Objective To estimate the pooled nonadherence rates and reasons for nonadherence to GLP‐1 agonists in overweight or patients with obesity participating in RCTs. Methods A systematic review and meta‐analysis of RCTs was conducted to evaluate nonadherence to GLP‐1 receptor agonists. A literature search was performed in PubMed, Embase, and Web of Science from inception to October 2, 2024. Studies were included if they evaluated GLP‐1 receptor agonists for overweight or obesity management and reported adherence outcomes. Results The pooled RR for nonadherence to GLP‐1 receptor agonists was 0.63 (95% CI: 0.48, 0.82, p = 0.01), indicating a 37% lower risk of nonadherence compared with the control group. However, ADR‐induced nonadherence was significantly higher in the GLP‐1 group (RR: 2.29 [95% CI: 1.47, 3.56, p = 0.04]), particularly due to gastrointestinal side effects. Nonadherence due to loss to follow‐up was lower in the GLP‐1 group (RR: 0.43 [95% CI: 0.27, 0.71, p = 0.18]). Conclusion GLP‐1 receptor agonists were associated with a lower overall nonadherence rate in RCTs compared with control treatments, suggesting higher persistence. However, ADR‐related nonadherence was significantly higher, particularly due to gastrointestinal side effects. These findings highlight the need for strategies to improve treatment tolerability and adherence in real‐world settings.