A comprehensive Bayesian network meta-analysis of 55 randomized trials involving 16,610 prediabetic adults reveals that GLP-1 receptor agonists and dual GIP/GLP-1 agonists deliver the most potent metabolic benefits. Semaglutide 2.4mg achieved remarkable 13.6kg average weight loss while reducing HbA1c by 0.39%. Tirzepatide 15mg demonstrated the strongest glucose control, lowering fasting plasma glucose by 9.58 mg/dL. These findings carry profound implications for the estimated 1.12 billion people worldwide with prediabetes, a population at high risk for diabetes progression. The magnitude of weight loss with semaglutide approaches that seen in bariatric surgery studies, representing a paradigm shift in prediabetes management. Unlike earlier diabetes prevention trials that relied primarily on metformin, this analysis establishes newer incretin-based therapies as potentially superior interventions. The safety profile across interventions was generally acceptable, though the analysis likely underestimates real-world adherence challenges and long-term effects. For clinical practice, these results suggest prediabetes warrants more aggressive pharmaceutical intervention than previously recognized, potentially preventing millions of diabetes cases globally while delivering substantial cardiovascular and metabolic co-benefits through dramatic weight reduction.