Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21(st) century

World J Gastroenterol. 2014 Sep 7;20(33):11467-85. doi: 10.3748/wjg.v20.i33.11467.


Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.

Keywords: Chronic pancreatitis; Clinical trials; Fat malabsorption; Lipase; Pancreatic enzyme replacement therapy; Pancreatic insufficiency; Steatorrhea.

Publication types

  • Historical Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antacids / therapeutic use
  • Chemistry, Pharmaceutical
  • Drug Therapy, Combination
  • Enzyme Replacement Therapy / history
  • Enzyme Replacement Therapy / trends*
  • Exocrine Pancreatic Insufficiency / diagnosis
  • Exocrine Pancreatic Insufficiency / drug therapy*
  • Exocrine Pancreatic Insufficiency / enzymology
  • Exocrine Pancreatic Insufficiency / history
  • Exocrine Pancreatic Insufficiency / physiopathology
  • Gastric Emptying / drug effects
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Hydrogen-Ion Concentration
  • Intestinal Absorption
  • Intestine, Small / drug effects
  • Intestine, Small / metabolism
  • Lipid Metabolism / drug effects
  • Pancreas, Exocrine / drug effects*
  • Pancreas, Exocrine / enzymology
  • Pancreas, Exocrine / physiopathology
  • Tablets, Enteric-Coated
  • Treatment Outcome


  • Antacids
  • Tablets, Enteric-Coated