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已发表论文
GLP-1 受体激动剂的长期疗效轨迹：一项系统评价和网络荟萃分析
Authors Li Z , Han Z, Sun R, Xuan X, Huang C
Received 16 May 2025
Accepted for publication 19 August 2025
Published 23 September 2025 Volume 2025:18 Pages 3611—3624
DOI https://doi.org/10.2147/DMSO.S539822
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Halis Kaan Akturk
Zixuan Li,1,* Zhoubo Han,1,* Rong Sun,2 Xiuping Xuan,3 Chenghu Huang1
1Department of Endocrinology, Bishan Hospital of Chongqing Medical University, Bishan, Chongqing, 402760, People’s Republic of China; 2Department of Ophthalmology, Taihe Hospital, Hubei University of Medical, Shiyan, Hubei, 442000, People’s Republic of China; 3Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Chenghu Huang, Department of Endocrinology, Bishan Hospital of Chongqing Medical University, Bishan, Chongqing, 402760, People’s Republic of China, Tel +86-023-41522901, Email chenghubs@163.com
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.
Keywords: glucagon-like peptide 1 receptor agonists, type 2 diabetes, network meta-analysis, systematic review
1Department of Endocrinology, Bishan Hospital of Chongqing Medical University, Bishan, Chongqing, 402760, People’s Republic of China; 2Department of Ophthalmology, Taihe Hospital, Hubei University of Medical, Shiyan, Hubei, 442000, People’s Republic of China; 3Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Chenghu Huang, Department of Endocrinology, Bishan Hospital of Chongqing Medical University, Bishan, Chongqing, 402760, People’s Republic of China, Tel +86-023-41522901, Email chenghubs@163.com
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.
Keywords: glucagon-like peptide 1 receptor agonists, type 2 diabetes, network meta-analysis, systematic review