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 (Φs) 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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