Introduction and Objective: Glucagon-like peptide-1-based treatments (GLP-1s) are increasingly prescribed for type 2 diabetes (T2D), and their clinical benefits depend on sustained treatment. While individual studies report low persistence and adherence, a comprehensive synthesis of evidence is lacking. This systematic literature review aimed to synthesize real-world persistence and adherence among adults with T2D initiating GLP-1 therapy. Methods: Following PRISMA guidelines, observational studies (2014-2025) reporting persistence (treatment gap thresholds ranging from 30-90 days) and/or adherence (proportion of days covered ≥80%) among adults with T2D initiating a GLP-1(tirzepatide, semaglutide, dulaglutide, liraglutide) in the United States were identified. Meta-analyses using restricted maximum likelihood random effects modeling were used to estimate overall pooled proportions and 95% confidence intervals (CI). Results: Twenty-eight studies including 267,542 patients were included. Overall, 69% (95% CI: 65%-73%) of patients were persistent at 6 months and 49% (95% CI: 43%-55%) at 12 months. At 12 months, dulaglutide demonstrated the highest persistence (56%, 95%CI: 55%-56%), followed by semaglutide (53%, 95%CI: 44%-62%) and liraglutide (43%, 95%CI: 30%-55%). Overall, 50% (95% CI: 45%-55%) of patients were adherent at 6 months and 42% (95% CI: 37%-47%) at 12 months. At 12 months, dulaglutide showed highest adherence (50%, 95%CI: 43%-56%) followed by semaglutide (43%, 95%CI: 41%-44%) and liraglutide (34%, 95%CI: 29%-39%). Conclusion: Despite the introduction of new GLP-1 agents, real world GLP-1 persistence and adherence remain consistently low across studies, indicating continued real-world barriers to sustained use. These findings highlight a critical unmet need for strategies that address barriers to sustained GLP-1 use to improve real-world effectiveness and patient outcomes.