A Comparison of the Effects of the GLP-1 Analogue Liraglutide and Insulin Glargine on Endothelial Function and Metabolic Parameters: A Randomized, Controlled Trial Sapporo Athero-Incretin Study 2 (SAIS2).
OBJECTIVE
GLP-1 improves hyperglycemia, and it has been reported to have favorable effects on atherosclerosis. However, it has not been fully elucidated whether GLP-1 is able to improve endothelial function in patients with type 2 diabetes. Therefore, we investigated the efficacy of the GLP-1 analogue, liraglutide on endothelial function and glycemic metabolism compared with insulin glargine therapy.


METHODS
In this multicenter, prospective randomized parallel-group comparison study, 31 diabetic outpatients (aged 60.3 ± 10.3 years with HbA1c levels of 8.6 ± 0.8%) with current metformin and/or sulfonylurea treatment were enrolled and randomly assigned to receive liraglutide or glargine therapy once daily for 14 weeks. Flow mediated dilation (FMD), a comprehensive panel of hemodynamic parameters (Task Force Monitor), and serum metabolic markers were assessed before and after the treatment period.


RESULTS
A greater reduction (worsening) in %FMD was observed in the glargine group, although this change was not statistically different from the liraglutide group (liraglutide; 5.7 to 5.4%, glargine 6.7 to 5.7%). The augmentation index, C-peptide index, derivatives of reactive oxygen metabolites and BMI were significantly improved in the liraglutide group. Central systolic blood pressure and NT-proBNP also tended to be improved in the liraglutide-treated group, while improvements in HbA1c levels were similar between groups. Cardiac index, blood pressure and most other metabolic parameters were not different.


CONCLUSIONS
Regardless of glycemic improvement, early liraglutide therapy did not affect endothelial function but may provide favorable effects on beta-cell function and cardioprotection in type 2 diabetics without advanced atherosclerosis.


BACKGROUND
UMIN Clinical Trials Registry System as trial ID UMIN000005331.
Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Hiroshi
H
Nomoto
Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Hideaki
H
Miyoshi
Department of Cardiovascular Medicine, NTT East Japan Sapporo Hospital, Sapporo, Japan; Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Tomoo
T
Furumoto
Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Interfaculty Initiative in Information Studies, The University of Tokyo, Tokyo, Japan.
Koji
K
Oba
Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Hiroyuki
H
Tsutsui
Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Arina
A
Miyoshi
Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Takuma
T
Kondo
Manda Memorial Hospital, Sapporo, Japan.
Kenichi
K
Tsuchida
Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Tatsuya
T
Atsumi
Manda Memorial Hospital, Sapporo, Japan.
Naoki
N
Manda
Kurihara Clinic, Sapporo, Japan.
Yoshio
Y
Kurihara
Aoki Clinic, Sapporo, Japan.
Shin
S
Aoki
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000150:complications; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004727:Endothelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000069036:Insulin Glargine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D000069450:Liraglutide / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D000069450:Liraglutide