37723
document
Treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin improves fasting islet-cell function in subjects with type 2 diabetes . CONTEXT Dipeptidyl peptidase 4 ( DPP-4 ) inhibitors are proposed to lower blood glucose in type 2 diabetes mellitus ( T2DM ) by prolonging the activity of the circulating incretins , glucose-dependent insulinotropic polypeptide ( GIP ) and glucagon-like peptide 1 ( GLP-1 ) . Consistent with this mechanism of action , DPP-4 inhibitors improve glucose tolerance after meals by increasing insulin and reducing glucagon levels in the plasma . However , DPP-4 inhibitors also reduce fasting blood glucose , an unexpected effect because circulating levels of active GIP and GLP-1 are low in the postabsorptive state . OBJECTIVE The objective of the study was to examine the effects of DPP-4 inhibition on fasting islet function . DESIGN We conducted a randomized , double-blind , placebo-controlled trial . SETTING The study was performed in General Clinical Research Centers at two University Hospitals . SUBJECTS Forty-one subjects with T2DM were treated with metformin or diet , having good glycemic control with glycosylated hemoglobin values of 6.2-7.5 % . INTERVENTION Subjects were treated with vildagliptin ( 50 mg twice daily ) or placebo for 3 months , followed by a 2-wk washout . Major Outcome Measure : We measured insulin secretion in response to iv glucose and arginine before and after treatment and after drug washout . RESULTS There were small and comparable reductions in glycosylated hemoglobin in both groups over 3 months . Vildagliptin increased fasting GLP-1 levels in subjects taking metformin , but not those managed with diet , and raised active GIP levels slightly . DPP-4 inhibitor treatment improved the acute insulin and C-peptide responses to glucose ( 50 and 100 % respectively ; P < 0.05 ) and increased the slope of the C-peptide response to glucose ( 33 % ; P = 0.023 ) . CONCLUSION Vildagliptin improves islet function in T2DM under fasting conditions . This suggests that DPP-4 inhibition has metabolic benefits in addition to enhancing meal-induced GLP-1 and GIP activity .
37724
Intervention_Pharmacological
dipeptidyl peptidase-4 inhibitor vildagliptin
37725
Intervention_Pharmacological
Dipeptidyl peptidase 4 ( DPP-4 ) inhibitors
37726
Intervention_Pharmacological
DPP-4 inhibitors
37727
Intervention_Pharmacological
DPP-4 inhibitors
37728
Intervention_Control
placebo-controlled
37729
Intervention_Pharmacological
metformin
37730
Intervention_Pharmacological
vildagliptin
37731
Intervention_Control
placebo
37732
Intervention_Pharmacological
metformin
37733
Intervention_Pharmacological
DPP-4 inhibitor
37734
Intervention_Pharmacological
Vildagliptin
37735
Outcome_Physical
effects of DPP-4 inhibition on fasting islet function
37736
Outcome_Physical
insulin secretion in response to iv glucose and arginine
37737
Outcome_Physical
glycosylated hemoglobin
37738
Outcome_Physical
GLP-1
37739
Outcome_Physical
acute insulin and C-peptide responses
37740
Outcome_Physical
C-peptide response