title: Effects of Liraglutide Monotherapy on Beta Cell Function and Pancreatic Enzymes Compared with Metformin in Japanese Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Subpopulation Analysis of the KIND-LM Randomized Trial.
abstract: OBJECTIVE
  Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming one of the major therapeutic options for the treatment of type 2 diabetes mellitus (T2DM). This study was conducted as an exploratory analysis to clarify the effects of liraglutide, a GLP-1RA, on beta cell function, fat distribution and pancreas volume compared with metformin in Japanese overweight/obese patients with T2DM.
  
  
  METHODS
  A subpopulation of the Keio study for Initial treatment of type 2 Diabetes with Liraglutide versus Metformin (KIND-LM) study participants (n = 20, 10 in oral metformin group and 10 in subcutaneous liraglutide group) who were enrolled at Keio University Hospital and underwent frequently sampled mixed meal tolerance test (MTT) and abdominal computed tomography (CT) at weeks 0 and 24 were included in this analysis. The patients were treated with either metformin or liraglutide throughout the 24-week study period.
  
  
  RESULTS
  Changes in glycemic parameters such as glycated hemoglobulin (HbA1c), glycated albumin and 1,5-anhydroglucitol at week 24 were comparable between the groups. An oral minimal model based on MTT revealed that static-phase beta cell responsiveness (Φ s) and static-phase disposition index were significantly increased at week 24 in the liraglutide group but not in the metformin group. There was no significant change in fat distribution as well as body weight at week 24 in either group. Serum amylase and lipase levels modestly but significantly increased in the liraglutide group during the study; however, there was no incidence of pancreatitis and pancreas volume was not changed in the liraglutide group.
  
  
  CONCLUSIONS
  Liraglutide monotherapy for 24 weeks improved beta cell responsiveness with no change in either body weight or fat distribution. Further investigation is needed to clarify the mechanism by which liraglutide increases serum pancreatic enzymes.
  
  
  BACKGROUND
  The University Hospital Medical Information Network (UMIN) Clinical Trials Registry ( http://www.umin.ac.jp/ctr/ ); UMIN000004243.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. momo2012kumi0124ko@gmail.com.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. ysaisho@keio.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Saisho
authors.affiliation: Institute for Chemical and Bioengineering, ETH Zurich, Zurich, Switzerland. erica.manesso@chem.ethz.ch.|Swiss Institute of Bioinformatics, Lausanne, Switzerland. erica.manesso@chem.ethz.ch.
authors.forename: Erica
authors.initials: E
authors.lastname: Manesso
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. tana176k@sepia.ocn.ne.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. shumeg1580083@yahoo.co.jp.
authors.forename: Shu
authors.initials: S
authors.lastname: Meguro
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. j-irie@z8.keio.jp.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Irie
authors.affiliation: Department of Radiology, Keio University School of Medicine, Tokyo, Japan. hsugiura@a6.keio.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sugiura
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. tkawai@keio.jp.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Department of Radiology, Keio University School of Medicine, Tokyo, Japan. jinzaki@rad.med.keio.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Jinzaki
authors.affiliation: Department of Information Engineering, University of Padua, Padua, Italy. cobelli@dei.unipd.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. hiito@z8.keio.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000681:Amylases / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D050218:Body Fat Distribution; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D008049:Lipase / Q000097:blood; D000069450:Liraglutide / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000188:drug therapy; D009929:Organ Size / Q000187:drug effects; D050177:Overweight / Q000150:complications* / Q000188:drug therapy; D011859:Radiography; D016896:Treatment Outcome
chemical_list: D000681:Amylases; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008049:Lipase; D000069450:Liraglutide; D008687:Metformin