Association of glucagon-like peptide-1 receptor agonist use with risk of infections: A systematic review and meta-analysis
S. S. Han, Yiwen Liu, Baodi Xing, Yucheng Yang, Zijun Liu, Yixuan Li, Xuechen Wang, Jie Yu, Fan Ping, Wei Li, Lingling Xu, Tao Qi, Yuelun Zhang, Yuxiu Li, Huabing Zhang
Abstract
OBJECTIVE: To assess whether GLP-1 RA treatment influences infection risk in randomized clinical trials (RCTs). METHODS: Systematic searches were conducted across PubMed, EMBASE, Cochrane Library, and Web of Science (inception to September 24, 2024), and reference lists of eligible articles. RCTs comparing GLP-1 RA treatment with placebo or non-GLP-1 RA treatments were included. Dual reviewer resolved disagreements by consensus. Two reviewers independently extracted data following PRISMA recommendations and assessed risk of bias via Cochrane tool. RESULTS: A total of 136 RCTs (n = 164,322) were included. GLP-1 RA treatment was associated with a significant reduction in serious infections (RR, 0.89; 95% CI, 0.86-0.93; absolute risk difference, -30 per 10,000 persons/year; I² = 0%), non-serious (RR, 0.90; 95% CI, 0.85-0.97; I² = 77%), and total infections (RR, 0.89; 95% CI, 0.84-0.94; I² = 77%). Reductions were observed for serious respiratory (RR, 0.84; 95% CI, 0.79-0.90), skin and subcutaneous (RR, 0.77; 95% CI, 0.68-0.87), musculoskeletal (RR, 0.79; 95% CI, 0.65-0.97), vascular (RR, 0.65; 95% CI, 0.47-0.90), and COVID-19 infections (RR, 0.82; 95% CI, 0.72-0.92), all with I² = 0%. Meta-regression showed greater weight loss (β = -0.011; P =.045), hemoglobin A1c reduction (β = -0.229; P =.026), and higher GLP-1 RA doses (RR, 0.87; 95% CI, 0.83-0.92) were associated with lower risk. CONCLUSION: GLP-1 RA use was associated with reduced risk of serious infections, particularly in respiratory, skin, musculoskeletal, vascular systems and COVID-19, partially explained by weight loss and improved glycemic control.