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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

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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.

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Acknowledgments

The authors acknowledge Ms. Emi Iwase, Tamami Someya and the staff of the Department of Internal Medicine, Keio University School of Medicine for their assistance, the staff of the Department of Laboratory Medicine, Keio University School of Medicine for their technical support, and Dr. Takayuki Abe, the Department of Preventive Medicine and Public Health, Center for Clinical Research, Keio University School of Medicine for his statistical advice. The authors also thank the KIND-LM study investigators for their constructive suggestions and Dr. Wendy Gray for editing the manuscript.

Author contributions

K T. and Y. S. researched data and wrote the manuscript. K. T., Y. S., T. K., M. T., S. M., J. I., T. I., T. S., J. M., K. Y., Y. A., I. T. and H. I. contributed to the discussion, and reviewed and edited the manuscript. Y. S. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Author notes

    Authors and Affiliations

    1. Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

      Kumiko Tanaka, Yoshifumi Saisho, Masami Tanaka, Shu Meguro, Junichiro Irie, Toshihide Kawai & Hiroshi Itoh

    2. Institute for Chemical and Bioengineering, ETH Zurich, Zurich, Switzerland

      Erica Manesso

    3. Swiss Institute of Bioinformatics, Lausanne, Switzerland

      Erica Manesso

    4. Department of Radiology, Keio University School of Medicine, Tokyo, Japan

      Hiroaki Sugiura & Masahiro Jinzaki

    5. Department of Information Engineering, University of Padua, Padua, Italy

      Claudio Cobelli

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    1. Kumiko Tanaka
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    On behalf of the KIND-LM study investigators

    Corresponding author

    Correspondence to Yoshifumi Saisho.

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    Declaration of interest

    The authors have no conflict of interest in the subject matter of the manuscript.

    Funding sources

    This study was sponsored by Keio University and was supported by Keio University’s general research funds. Keio University received unrestricted donations from Novo Nordisk Pharma Limited and from other pharmaceutical manufacturers. A portion of these combined donations contributed to covering the university’s research-related expenses. The authors take full responsibility for the protocol design, study conduct and content of this manuscript.

    Ethical approval

    All procedures in this study were in accordance with the 1964 Helsinki declaration, and this study was approved by the Ethical Committee of the Keio University School of Medicine.

    Informed consent

    Written informed consent was obtained from all study patients.

    Additional information

    K. Tanaka and Y. Saisho contributed equally.

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    Cite this article

    Tanaka, K., Saisho, Y., Manesso, E. et al. 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. Clin Drug Investig 35, 675–684 (2015). https://doi.org/10.1007/s40261-015-0331-5

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