Abstract
Objective: Fibroblast growth factor 21 (FGF21) analogs have been used to improve glucose homeostasis and lipid metabolism; however, their effects remain contentious. The present meta-analysis aimed to review the effects and safety of FGF21 analogs on glycemic parameters, lipid profiles, and adiponectin (ADP) levels in overweight or obese adults. Methods: A systematic literature search for randomized controlled trials (RCTs) was conducted up to June 2025. A random-effects model or a common-effect model was used to calculate the mean difference (MD) or standardized MD (SMD), along with the corresponding 95% confidence intervals (CIs). Results: This meta-analysis including 11 RCTs showed that FGF21 analogs reduced triglycerides (MD = -59.33 mg/dL, 95% CI = -84.61 to -34.04), total cholesterol (MD = -17.14 mg/dL, 95% CI = -25.11 to -9.18), and low-density lipoprotein cholesterol (MD = -10.50 mg/dL, 95% CI = -14.42 to -6.59). Furthermore, FGF21 analogs increased high-density lipoprotein cholesterol (MD = 10.64 mg/dL, 95% CI = 6.23-15.05) and circulating ADP (MD = 3.18 μg/mL, 95% CI = 1.94-4.42). However, FGF21 analogs had no effect on fasting glucose (SMD = -0.22, 95% CI = -0.52 to 0.07) or insulin concentrations (SMD = -0.49, 95% CI = -1.04 to 0.06). Subgroup analyses revealed that the lipid-lowering effects varied among different FGF21 analogs. FGF21 treatment did not show any statistically significant difference in the incidence of serious side effects. Conclusions: We identified significant favorable effects of FGF21 analogs in improving lipid profiles and elevating circulating ADP levels in overweight and obese adults. Future studies are needed to evaluate the clinical benefits in this area of research.