title: Pancreatic Effects of Liraglutide or Sitagliptin in Overweight Patients With Type 2 Diabetes: A 12-Week Randomized, Placebo-Controlled Trial.
abstract: To assess the mechanistic effects of the glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide and the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin on (exocrine) pancreatic physiology and morphology.
  
  
  
  For this randomized, double-blind, parallel-group trial, 55 patients with type 2 diabetes treated with metformin and/or sulfonylurea agents were included. Participants received liraglutide 1.8 mg (n= 19), sitagliptin 100 mg (n= 19), or matching placebos (n= 17) once daily for 12 weeks. The primary end point was change in exocrine function (intraduodenal pancreatic fluid secretion, lipase activity, fecal elastase-1, and chymotrypsin). Secondary end points included changes in plasma enzyme concentrations and pancreatic morphology (per MRI).
  
  
  
  No patient developed pancreatitis. Sitagliptin increased intraduodenal pancreatic fluid secretion by 16.3 mL (95% CI -0.3 to 32.9;P= 0.05), whereas liraglutide did not change exocrine pancreatic function. Neither therapy increased lipase/amylase levels after 12 weeks. However, liraglutide increased lipase levels after 6 weeks (23.5 U/L [95% CI 2.1-44.8];P= 0.03) and sitagliptin increased amylase levels after 2 and 6 weeks (13.7 U/L [95% CI 3.4-23.9];P= 0.03). Both drugs increased plasma trypsinogen after 12 weeks (liraglutide: 34.6 µg/mL [95% CI 15.1-54.2],P= 0.001; sitagliptin: 23.9 µg/mL [95% CI 4.9-42.9],P= 0.01). Neither changed pancreatic morphology, although liraglutide tended to increase pancreatic volume (7.7 cm3[95% CI -1.2 to 16.6];P =0.09). Treatment-induced volume expansion was associated with increased amylase levels.
  
  
  
  A 12-week treatment with liraglutide or sitagliptin only resulted in a brief and modest increase of plasma pancreatic enzyme concentrations in patients with type 2 diabetes. Apart from a minimal sitagliptin-induced increase in intraduodenal fluid secretion, pancreatic exocrine function was unaffected. The long-term clinical consequences of these discrete changes require further study.
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands mm.smits1@vumc.nl.
authors.forename: Mark M
authors.identifier: 0000-0001-8236-8842
authors.initials: MM
authors.lastname: Smits
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Lennart
authors.initials: L
authors.lastname: Tonneijck
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Marcel H A
authors.initials: MH
authors.lastname: Muskiet
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Mark H H
authors.initials: MH
authors.lastname: Kramer
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Indra C
authors.initials: IC
authors.lastname: Pieters-van den Bos
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Karuna E W
authors.initials: KE
authors.lastname: Vendrik
authors.affiliation: Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, the Netherlands.|Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Trynke
authors.initials: T
authors.lastname: Hoekstra
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Bruno
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Daniël H
authors.initials: DH
authors.lastname: van Raalte
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Djuna L
authors.initials: DL
authors.lastname: Cahen
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008049:Lipase / Q000097:blood; D000069450:Liraglutide / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D050177:Overweight / Q000150:complications; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D000068900:Sitagliptin Phosphate / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014362:Trypsinogen / Q000097:blood / Q000652:urine; D044465:White People; D000516:alpha-Amylases / Q000097:blood; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D014362:Trypsinogen; D008687:Metformin; D008049:Lipase; D000516:alpha-Amylases; D000068900:Sitagliptin Phosphate; D000097789:Glucagon-Like Peptide-1 Receptor Agonists