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.
GLP-1 Therapies