Liraglutide, a glucagon-like peptide-1 analog, increased insulin sensitivity assessed by hyperinsulinemic-euglycemic clamp examination in patients with uncontrolled type 2 diabetes mellitus.
OBJECTIVE
Glucagon-like peptide-1 (GLP-1) analog promotes insulin secretion by acting on pancreatic β-cells. This antihyperglycemic treatment for type 2 diabetes mellitus (DM) has attracted increased clinical attention not only for its antihyperglycemic action but also for its potential extrapancreatic effects. We investigated whether liraglutide, a GLP-1 analog, could enhance insulin sensitivity as assessed by the hyperinsulinemic-euglycemic clamp in type 2 DM patients.


METHODS
We prospectively enrolled 31 uncontrolled type 2 DM patients who were hospitalized and equally managed by guided diet- and exercise-therapies and then introduced to either liraglutide- or intensive insulin-therapy for 4 weeks. Insulin sensitivity was assessed by the glucose infusion rate (GIR) using hyperinsulinemic-euglycemic clamp before and after the therapies.


RESULTS
Values of HbA1c, postprandial plasma glucose, and body mass index (BMI) were significantly decreased by hospitalized intensive insulin-therapy or liraglutide-therapy. GIR was significantly increased by liraglutide-therapy but not by insulin-therapy, indicating that liraglutide-therapy significantly enhanced insulin sensitivity. BMI decreased during liraglutide-therapy but was not significantly correlated with changes in GIR. Multivariate logistic regression analysis demonstrated that liraglutide-therapy significantly correlated with increased insulin sensitivity in uncontrolled DM patients.


CONCLUSIONS
Liraglutide may exhibit favorable effects on diabetes control for type 2 DM patients by increasing insulin sensitivity as an extrapancreatic action. Clinical trial registration Unique Identifier is UMIN000015201.
Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto 862-0976, Japan ; Division of Preventive Cardiology, Department of Cardiovascular Medicine, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto 860-8556, Japan ; Diabetes Care Center, Cardiovascular Division, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto 862-0976, Japan.
Hideaki
0000-0002-7391-7966
H
Jinnouchi
Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto 862-0976, Japan ; Diabetes Care Center, Cardiovascular Division, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto 862-0976, Japan ; Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Science, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
Seigo
0000-0003-2494-0374
S
Sugiyama
Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto 862-0976, Japan.
Akira
0000-0002-5463-6114
A
Yoshida
Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto 862-0976, Japan.
Kunio
0000-0002-7786-4646
K
Hieshima
Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto 862-0976, Japan.
Noboru
N
Kurinami
Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto 862-0976, Japan.
Tomoko
0000-0002-3986-8291
T
Suzuki
Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto 862-0976, Japan.
Fumio
0000-0003-3385-2421
F
Miyamoto
Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto 862-0976, Japan.
Keizo
0000-0003-3779-1638
K
Kajiwara
Department of Community Medicine, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
Kunihiko
0000-0002-3750-3440
K
Matsui
Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto 862-0976, Japan ; Diabetes Care Center, Cardiovascular Division, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto 862-0976, Japan.
Tomio
0000-0002-4370-4521
T
Jinnouchi
D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy; D004032:Diet; D004035:Diet Therapy; D015444:Exercise; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives*; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000378:metabolism; D006760:Hospitalization; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008019:Life Style; D000069450:Liraglutide / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies
D052216:Glucagon-Like Peptide 1; D005947:Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D000069450:Liraglutide; C517652:hemoglobin A1c protein, human