The effect of Pemafibrate on glucose metabolism and FGF21: a systematic review and meta-analysisa of randomized...

Pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) modulator, has shown potential in improving metabolic parameters. However, its effects on key metabolic biomarkers and fibroblast growth factor 21 (FGF21), have not been fully elucidated. To evaluate the effects of Pemafibrate on fasting blood glucose (FBG), insulin, HbA1c, HOMA-IR, and FGF21 through a systematic review and meta-analysis of randomized controlled trials (RCTs).

A comprehensive literature search was conducted in PubMed, Web of Science, SCOPUS, and Embase databases from their inception until November 2025. RCTs assessing the effects of Pemafibrate on the selected metabolic biomarkers were included and the weighted mean differences (WMD) for each outcome were calculated using a random-effects model.

A total of 14 RCTs with 4084 participants were included in the present meta-analysis. Pemafibrate significantly reduced FBG (11 studies, 3273 patients, WMD = -0.47 mmol/L, 95% CI: -0.70 to -0.24), insulin levels (7 studies, 2102 patients, WMD = -30.72 pmol/L, 95% CI: -42.08 to -19.36), and HOMA-IR (8 studies, 2381 patients, WMD = -1.60, 95% CI: -2.27 to -0.93). Additionally, FGF21 levels were significantly increased (7 studies, 2178 patients, WMD = 3.30 pg/mL, 95% CI: 2.57 to 4.04). The effect on HbA1c was marginally non-significant (10 studies, 3065 patients, WMD = 0.02%, 95% CI: 0.00 to 0.05). Subgroup analysis revealed that lower duration of Pemafibrate intake were associated with significant improvements in FBG, while higher doses (> 0.2 mg/day) had more pronounced effects on FGF21 and glucoe metabolism. Meta-regression indicated that treatment duration was positively correlated with reductions in insulin levels. The overall GRADE quality assessment was rated as very good, supporting a moderate-to-high level of confidence.

Pemafibrate significantly improves glucose metabolism, insulin sensitivity, and increases FGF21 levels, making it a promising therapeutic option for patients with metabolic disorders.