Long-Term Efficacy Trajectories of GLP-1 Receptor Agonists: A Systematic Review and Network Meta-Analysis
Zixuan Li, Zhoubo Han, Rong Sun, Xiuping Xuan, Chenghu Huang
Abstract
Purpose: To investigate the long-term efficacy and changing trajectories of glucagon-like peptide-1 receptor agonists (GLP-1RAs) among patients with type 2 diabetes. Methods: The PubMed, Embase and Cochrane Library databases were searched up to March 2024 to identify randomized controlled trials that assessed the efficacy of GLP-1RAs compared with placebo. To further explore the long-term trajectories of GLP-1RAs, we also conducted subgroup analyses of the placebo-subtracted groups based on the follow-up periods: 12-18 weeks, 24-30 weeks, 48-56 weeks, 68-78 weeks and ≥ 104 weeks. Results: Fifty-five trials involving 18,876 participants were included in this meta-analysis. GLP-1RAs significantly improved HbA1c levels, body weight, fasting plasma glucose (FPG), systolic blood pressure, and serum lipid levels. GLP-1RAs continuously reduced HbA1c and FPG for at least 104 weeks, with the largest reductions observed at 12-18 weeks (versus placebo, WMD -0.99 [-1.09, -0.89], P < 0.001; -1.56 [-1.82. -1.29], P < 0.001, respectively). However, the reductions in HbA1c and FPG at ≥ 104 weeks were approximately 0.36% and 0.47 mmol/L less than the reductions at 12-18 weeks, respectively. With respect to weight loss, the optimal effect was observed at 24-30 weeks (WMD -2.42 [-2.90, -1.95], P < 0.001), followed by a plateau period. In addition, GLP-1RAs were associated with a greater risk of hypoglycemia and gastrointestinal adverse events. Conclusion: GLP-1RAs are recommended for long-term treatment of patients with type 2 diabetes due to the persistent improvement in glycemic control and weight loss. However, it is important to account for the weakening effects after 2 years.