7675 The Effects of Fibroblast Growth Factor-21 Analogues in Patients with Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Cardoso Jorge Henrique Cavalcanti Orestes , Sudo Renan Yuji Ura , Souza Maria Eduarda Cavalcanti , Pessôa Felipe Dircêu Dantas Leite , de Moraes Francisco Cezar Aquino , de Oliveira Natalia Menezes Nunes , Kelly Francinny Alves , Lopes Lucca Moreira , Lima Pedro Lucas Gomes , Barros Maria Luísa Siegloch , Bandeira Francisco Farias 
Published: October 2024

Abstract
Disclosure: J.C. Cardoso: None. R.Y. Ura Sudo: None. M.C. Souza: None. F.D. Pessôa: None. F.A. Moraes: None. N.M. Oliveira: None. F.A. Kelly: None. L.M. Lopes: None. P.G. Lima: None. M.S. Barros: None. F.F. Bandeira: None.
Fibroblast growth factor 21 (FGF-21), a potent insulin sensitizer, has been shown to improve lipid profile, glucose metabolism and energy expenditure. The FGF-21 analogues emerged as a promising treatment avenue for critical components of metabolic syndrome, such as metabolic dysfunction associated steatohepatitis, hypertriglyceridemia, diabetes, and obesity. However, their potential treatment effects remain unclear. We systematically searched Pubmed, Web of Science, and Cochrane databases, from inception to January 2024, for randomized controlled trials (RCT) comparing the effects of FGF-21 analogues on glycemic control and lipid profile against placebo. Statistical analysis was performed in R software 4.3.1. A random-effects model was employed to compute mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI) for continuous and binary endpoints, respectively. A p-value of &lt; 0.05 was considered statistically significant. Heterogeneity was examined with the Cochran Q test, prediction interval and I² statistics. The results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guideline. The protocol was prospectively registered in PROSPERO under CRD42023493083 identification number. A total of 15 RCTs with 1427 patients were included, of whom 1038 (72.7%) were randomized to FGF-21 analogues therapy. The mean age was 55 years and the mean body mass index (Kg/m^2) was 35.2. Over a mean follow-up time of 20.8 weeks, the FGF-21 group presented a significant decrease in body weight (MD -0.75%; 95% CI -1.25 to -0.24; p=0.004; I²=0%), serum trigliceryde (MD -22.76%; 95% CI -30.48 to -15.04; p&lt;0.001; I²=62%), LDL-C (MD -5.46%; 95% CI -9.73 to -1.19; p=0.012; I²=33%), nonHDL-C (MD -10.65%; 95% CI -14.13 to -7.17; p&lt;0.001; I²=0%) and a significant increase in HDL-C (MD 10.50%; 95% CI 6.70 to 14.30; p&lt;0.001; I²=67%) and adiponectin (MD 18.80%; 95% CI 10.26 to 27.33; p&lt;0.001; I²=88%). Despite these favorable outcomes over placebo, the FGF-21 analogues caused nonsignificant decreases in HOMA-IR (MD -1.38; 95% CI -4.69 to 1.92; p=0.412; I²=85%), HbA1c (MD -0.52%; 95% CI -1.45 to 0.41; p=0.275; I²=99%), plasma glucose (MD -0.45 mg/dL; 95% CI -3.99 to 3.08; P = 0.802; I²=15%), plasma insulin (MD -7.24%; 95% CI -19.16 to 4.68; p=0.234; I²=0%), C peptide (MD -0.37 nmol/L; 95% CI -0.86 to 0.10; P = 0.126; I²=78%) and apolipoprotein B (MD -2.36%; 95% CI -26.45 to 21.72; p=0.848, I²=93%). In conclusion, the use of FGF-21 analogues led to significant improvements in the lipid profile without changes in glycemic control.
Presentation: 6/3/2024