ABSTRACT
The study compared effectiveness of intranasal administration of glypin (human recombinant modified glucagon-like peptide-1) and reference drug Victoza in BALB/c mice. The minimum effective dose of intranasal glypin was 0.5 mg/kg, and a 2-fold elevation of this dose increased the parameters of glypin activity up to the maximal levels. During the first 2 h after intranasal administration, the effectiveness of glypin greatly surpassed that of Victoza. Duration of action and the time course of antihyperglycemic activity of intranasal glypin (1 mg/kg) matched to the best parameters attained during its subcutaneous application. A high effectiveness of intranasal glypin opens the vistas to its further examination and employment.
Subject(s)
Blood Glucose/drug effects , Hypoglycemic Agents/administration & dosage , Tropanes/administration & dosage , Administration, Intranasal , Animals , Blood Glucose/metabolism , Dose-Response Relationship, Drug , Female , Glucagon-Like Peptide 1/agonists , Glucagon-Like Peptide 1/analogs & derivatives , Glucose Tolerance Test , Glycemic Control , Hyperglycemia/blood , Hyperglycemia/chemically induced , Hyperglycemia/drug therapy , Hypoglycemic Agents/pharmacology , Liraglutide/administration & dosage , Liraglutide/analogs & derivatives , Mice , Mice, Inbred BALB C , Recombinant Proteins/administration & dosage , Time Factors , Tropanes/pharmacologyABSTRACT
OBJECTIVES: 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. MATERIALS AND 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. TRIAL REGISTRATION: UMIN Clinical Trials Registry System as trial ID UMIN000005331.
