Effect of GLP-1 agonists on testosterone levels: a systematic review and meta-analysis.

INTRODUCTION: Testosterone plays a central role in endocrine and metabolic functions. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely prescribed for type 2 diabetes and obesity, have been proposed to modulate testosterone levels. Although this association is not yet covered by clinical guidelines, emerging studies suggest favorable effects, possibly due to weight loss and improved insulin sensitivity. This systematic review and meta-analysis aim to synthesize current evidence on how GLP-1 RAs influence testosterone levels and highlight areas for future investigation. MATERIALS AND METHODS: A systematic search was conducted using Embase, PubMed, Scopus, Cochrane, and Google Scholar databases through December 2024. Eligible studies included RCTs, cohort studies, and retrospective analyses comparing testosterone levels before and after GLP-1 RA administration. Primary and secondary outcomes included total, free, and bioavailable testosterone, SHBG, and HbA1c. All included studies reported baseline hormone values and used validated measurement techniques. Data analysis was performed using RStudio. RESULTS: Four studies comprising 219 patients pre-treatment and 216 post-treatment were included. GLP-1 RA use was significantly associated with increased bioavailable testosterone (MD -57.18; 95% CI -87.60 to -26.76; p < 0.001; I2 = 86%) and decreased HbA1c (MD 0.79; 95% CI 0.58 to 1.00; p < 0.001; I2 = 0%). Free testosterone (MD -1.62; p = 0.051) and SHBG (MD -6.62; p = 0.120) showed no significant changes. Sensitivity and Baujat analyses were used to explore heterogeneity. CONCLUSIONS: GLP-1 RAs appear to elevate bioavailable testosterone and improve glycemic control, while effects on free testosterone and SHBG remain inconclusive. These findings suggest possible endocrine benefits of GLP-1 therapy; however, further well-powered studies are warranted.