Kumiko Tanaka1, Yoshifumi Saisho2, Erica Manesso3,4, Masami Tanaka5, Shu Meguro6, Junichiro Irie7, Hiroaki Sugiura8, Toshihide Kawai9, Masahiro Jinzaki10, Claudio Cobelli11, Hiroshi Itoh12. 1. Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. momo2012kumi0124ko@gmail.com. 2. Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. ysaisho@keio.jp. 3. Institute for Chemical and Bioengineering, ETH Zurich, Zurich, Switzerland. erica.manesso@chem.ethz.ch. 4. Swiss Institute of Bioinformatics, Lausanne, Switzerland. erica.manesso@chem.ethz.ch. 5. Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. tana176k@sepia.ocn.ne.jp. 6. Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. shumeg1580083@yahoo.co.jp. 7. Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. j-irie@z8.keio.jp. 8. Department of Radiology, Keio University School of Medicine, Tokyo, Japan. hsugiura@a6.keio.jp. 9. Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. tkawai@keio.jp. 10. Department of Radiology, Keio University School of Medicine, Tokyo, Japan. jinzaki@rad.med.keio.ac.jp. 11. Department of Information Engineering, University of Padua, Padua, Italy. cobelli@dei.unipd.it. 12. Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. hiito@z8.keio.jp.
Abstract
BACKGROUND AND 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. CONCLUSION: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. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trials Registry ( http://www.umin.ac.jp/ctr/ ); UMIN000004243.
RCT Entities:
BACKGROUND AND 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/obesepatients 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. CONCLUSION: 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. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trials Registry ( http://www.umin.ac.jp/ctr/ ); UMIN000004243.
Authors: Chiara Dalla Man; Francesco Micheletto; Airani Sathananthan; Robert A Rizza; Adrian Vella; Claudio Cobelli Journal: Am J Physiol Endocrinol Metab Date: 2010-02-23 Impact factor: 4.310
Authors: Amy G Egan; Eberhard Blind; Kristina Dunder; Pieter A de Graeff; B Timothy Hummer; Todd Bourcier; Curtis Rosebraugh Journal: N Engl J Med Date: 2014-02-27 Impact factor: 91.245
Authors: Silvio E Inzucchi; Richard M Bergenstal; John B Buse; Michaela Diamant; Ele Ferrannini; Michael Nauck; Anne L Peters; Apostolos Tsapas; Richard Wender; David R Matthews Journal: Diabetes Care Date: 2015-01 Impact factor: 19.112
Authors: N Sarwar; P Gao; S R Kondapally Seshasai; R Gobin; S Kaptoge; E Di Angelantonio; E Ingelsson; D A Lawlor; E Selvin; M Stampfer; C D A Stehouwer; S Lewington; L Pennells; A Thompson; N Sattar; I R White; K K Ray; J Danesh Journal: Lancet Date: 2010-06-26 Impact factor: 202.731