The pharmaceutical use of lipases related to the Thermomyces lanuginosus (Humicola lanuginosa) lipase comprising amino acids 1-269 of SEQ ID NO: 2, with at least substitutions N33Q, T231R, N233R and D254S optionally in combination with a protease and/or an amylase. Examples of medical indications are: Treatment of digestive disorders, pancreatic exocrine insufficiency (PEI), pancreatitis, cystic fibrosis, diabetes type I, and/or diabetes type II. The lipases of the invention have, e.g., an improved digestion performance in vitro, an improved activity at a pH in the neutral range, an improved stability at low pH, are stable against protease-degradation, and/or are stable in the presence of pepsin and bile salts. The invention also relates to methods of determining digestion performance in vitro of lipases, as well as to certain novel variants of the lipase of T. lanuginosus.
