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

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.

• Authors: Kumiko Tanaka, Yoshifumi Saisho, Erica Manesso, Masami Tanaka, Shu Meguro, Junichiro Irie, Hiroaki Sugiura, Toshihide Kawai, Masahiro Jinzaki, Claudio Cobelli, Hiroshi Itoh, KIND-LM Study Investigators
• Journal: Clinical drug investigation (Clin Drug Investig) Vol. 35 Issue 10 Pg. 675-84 (Oct 2015) ISSN: 1179-1918 [Electronic] New Zealand
• PMID: 26369653 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Liraglutide
• Metformin
• Lipase
• Amylases

Topics

• Amylases (blood)
• Blood Glucose (drug effects)
• Body Fat Distribution
• Body Weight (drug effects)
• Diabetes Mellitus, Type 2 (complications, diagnostic imaging, drug therapy, pathology)
• Drug Administration Schedule
• Female
• Glycated Hemoglobin (metabolism)
• Humans
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Insulin Resistance
• Insulin-Secreting Cells (cytology, drug effects, enzymology)
• Lipase (blood)
• Liraglutide (pharmacology, therapeutic use)
• Male
• Metformin (pharmacology, therapeutic use)
• Middle Aged
• Obesity (complications, drug therapy)
• Organ Size (drug effects)
• Overweight (complications, drug therapy)
• Radiography
• Treatment Outcome