Pemafibrate for hypertriglyceridemia: a meta-analysis of randomized controlled trials evaluating efficacy and safety outcomes

Pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPAR-α) modulator, has been investigated for its effects on triglyceride (TG) levels and adverse events, particularly hepatic, renal, and musculoskeletal complications. This meta-analysis evaluates the safety and efficacy of pemafibrate across different doses and statin-use conditions. To assess the impact of pemafibrate on triglyceride levels and the incidence of adverse events, including hepatic, renal, and musculoskeletal complications, in a pooled population from multiple studies. A systematic review and meta-analysis was conducted, including randomized controlled trials (RCTs) and observational studies evaluating pemafibrate’s effects on TG levels and adverse events. Primary outcomes included overall TG levels, TG levels with and without statins, and adverse events. A total of 11,547 participants were included, with subgroup analyses for hepatic, renal, and musculoskeletal adverse events (n = 10,648), TG levels with and without statins (n = 11,210), and dose-dependent effects of pemafibrate (n = 509). Statistical heterogeneity and publication bias were assessed. Nine RCTs were included. Pemafibrate was associated with reductions in triglyceride (TG) levels compared with placebo (SMD −0.87; 95% CI −1.07 to −0.67; p = 0.00001), supported by moderate-certainty evidence. Subgroup analyses suggested greater TG reductions in patients not receiving statins (SMD −1.31; 95% CI −1.62 to −1.00) and those receiving statins (SMD −0.70; 95% CI −0.74 to −0.66), both high-certainty evidence. No clinically meaningful difference was observed between 0.2 and 0.4 mg doses (high-certainty evidence). Regarding safety, pemafibrate was associated with a slight increase in renal adverse events (moderate-certainty evidence). Musculoskeletal and hepatic adverse events did not appear to differ from placebo (moderate-certainty evidence), while overall adverse events were similar (high-certainty evidence). Pemafibrate appears to reduce triglyceride levels, with high-certainty evidence for subgroup comparisons and moderate-certainty evidence overall. Safety outcomes were generally similar to placebo, although a small increase in renal adverse events warrants careful monitoring. Dose-comparison findings are based on limited data and should be considered hypothesis-generating. Overall, pemafibrate may have a lipid-modifying effect, but clinical implications remain uncertain, and further large, long-term studies are needed.