Time Course and Comparative Risk of Hypophosphatemia After Ferric Carboxymaltose versus Ferric Derisomaltose: A Systematic Review, Meta-analysis, and Clinical Cost Considerations

Objectives: To compare the risk of hypophosphatemia and associated outcomes following ferric carboxymaltose (FCM) versus ferric derisomaltose (FDI) in adults with iron deficiency anemia. Methods: We conducted a systematic review and meta-analysis of studies identified through database searches up to November 2025. Randomized and observational studies comparing FCM and FDI were included. The primary outcome was the incidence of hypophosphatemia within 35 to 42 days after infusion. Secondary outcomes included severe and persistent hypophosphatemia, patient-reported outcomes, and economic outcomes. Data from randomized trials were quantitatively pooled using a random-effects model to calculate risk ratios (RRs) with 95% confidence intervals (CIs), whereas findings from observational and economic studies were summarized narratively. Results: Twenty-one studies were included, comprising 3 randomized controlled trials (364 participants) and 18 observational or economic evaluation studies. In pooled randomized comparisons, FCM was associated with a higher risk of hypophosphatemia within 35 to 42 days than FDI (RR 8.37, 95% CI 5.10-13.75; P < .00001; I 2 = 0%). Severe hypophosphatemia occurred in 11.3% of patients receiving FCM and was not observed with FDI. Persistent hypophosphatemia beyond 5 to 8 weeks was more frequent with FCM. Fatigue scores improved more with FDI. Economic evaluations reported greater quality-adjusted life years and lower healthcare costs with FDI. Conclusion: Ferric carboxymaltose is associated with a higher risk of hypophosphatemia compared with ferric derisomaltose. Ferric derisomaltose demonstrates a more favorable safety profile and consistent economic findings.