Efficacy of pancreatic enzyme replacement therapy on exocrine pancreatic insufficiency: a systematic review and meta-analysis
In brief
Enzyme replacement lifts fat absorption by 1.5 SDs in EPI patients
A meta-analysis of 14 randomized trials (684 patients) found pancreatic enzyme replacement therapy markedly improved nutrient uptake, raising the coefficient of fat absorption by about one and a half standard deviations and protein absorption by a similar magnitude versus placebo. Benefits were seen in cystic fibrosis and chronic pancreatitis subgroups, confirming PERT as a core treatment, though long-term clinical outcomes remain to be defined.
- Journal
- European journal of gastroenterology & hepatology (Q2)
- Published
- 12 June 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Xiuming Yang, Lina Yang, Weiwei Zhang, Lixia Zhong, Yulin Zheng
- PMID
- 42467921
- DOI
- 10.1097/MEG.0000000000003225
Why clinicians should know about it
- Picked for Gastroenterology (top studies of the week, 19 July 2026): Systematic review of pancreatic enzyme therapy efficacy
- Picked for Hepatology (top studies of the week, 19 July 2026).
Abstract
Exocrine pancreatic insufficiency (EPI) results in impaired digestion of fat, protein, and carbohydrates due to inadequate pancreatic enzyme secretion and is commonly managed with pancreatic enzyme replacement therapy (PERT). However, the extent to which PERT improves objective measures of nutrient absorption across different etiologies of EPI has not been fully clarified. A comprehensive search of PubMed/MEDLINE, Embase, Scopus, Web of Science, the Cochrane Library, and Google Scholar was performed from inception through December 2025. Randomized controlled trials (RCTs) comparing PERT with placebo in patients diagnosed with EPI were included. Eligible studies were required to report data on the coefficient of fat absorption (CFA) and the coefficient of nitrogen absorption (CNA). Data were pooled using a random-effects model, and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Subgroup, sensitivity, and publication bias analyses were performed. Fourteen RCTs involving 684 patients were included. PERT significantly improved fat absorption compared with placebo (CFA: SMD = 1.57, 95% CI: 1.20-1.94) and also enhanced protein absorption (CNA: SMD = 1.52, 95% CI: 0.97-2.06). Etiology-based subgroup analyses showed significant improvements in CFA among patients with cystic fibrosis (CF)-related EPI (SMD = 1.87, 95% CI: 1.48-2.25) and chronic pancreatitis-related EPI (SMD = 1.08, 95% CI: 0.67-1.49). Similarly, PERT significantly increased CNA in CF-associated EPI (SMD = 1.90, 95% CI: 1.30-2.50) and in EPI secondary to chronic pancreatitis (SMD = 0.74, 95% CI: 0.31-1.18). PERT substantially improves both fat and protein absorption in patients with EPI, with consistent efficacy across major etiological subgroups. These findings reinforce the role of enzyme replacement therapy as a cornerstone of EPI management and support its continued use to optimize digestive and nutritional outcomes.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.