INTRODUCTION: Incretin-based therapies, that is, @entity8142 agonists and @entity5735 inhibitors, are relatively novel antihyperglycaemic drugs that are frequently used in @entity164 2 @entity6 management. Apart from @entity413 -lowering, these agents exhibit pleiotropic actions that may have favourable and unfavourable clinical consequences. Incretin-based therapies have been associated with heart rate acceleration, @entity712 , @entity810 and acute @entity788 . Conversely, these agents may reduce blood pressure, glomerular hyperfiltration, @entity633 and @entity1560 . While large-sized cardiovascular safety trials can potentially identify the clinical significance of some of these pleiotropic actions, small-sized mechanistic studies are important to understand the (patho)physiological rationale of these findings. The current protocol describes a mechanistic study to assess cardiovascular, renal and gastrointestinal effects, and mechanisms of incretin-based therapies in @entity164 2 @entity6 . METHODS AND ANALYSES: 60 @entity1 with @entity164 2 @entity6 will undergo acute and prolonged randomised, double-blind, intervention studies. The acute intervention will consist of intravenous administration of the @entity8142 agonist exenatide or placebo. For the prolonged intervention, @entity1 will be randomised to 12-week treatment with the @entity8142 agonist liraglutide, the @entity5735 inhibitor @entity12350 or matching placebos. For each examined organ system, a primary end point is defined. Primary cardiovascular end point is change in resting heart rate variability assessed by beat-to-beat heart rate monitor and spectral analyses software. Primary renal end point is change in glomerular filtration rate assessed by the classic inulin clearance methodology. Primary gastrointestinal end points are change in pancreatic exocrine function assessed by MRI-techniques (acute intervention) and faecal @entity23606 levels (12-week intervention). Secondary end points include systemic haemodynamics, microvascular function, effective renal plasma flow, renal tubular function, pancreatic volume and gallbladder emptying-rate. MEDICAL ETHICS AND DISSEMINATION: The study is approved by the local Ethics Review Board (VU University Medical Center, Amsterdam) and conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. TRIAL REGISTRATION NUMBER: NCT01744236.

Cardiovascular, renal and gastrointestinal effects of incretin-based therapies: an acute and 12-week randomised, double-blind, placebo-controlled, mechanistic intervention trial in XXXX 2 @entity6 .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity788 :: ('MESH:D010190', 'Disease') :: ['pancreatitis'] @entity712 :: ('MESH:D006333', 'Disease') :: ['heart failure'] @entity5735 :: ('1803', 'Gene') :: ['DPP-4', 'dipeptidyl peptidase (DPP)-4'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes'] @entity1560 :: ('MESH:D005234', 'Disease') :: ['hepatic steatosis'] @entity633 :: ('MESH:D000419', 'Disease') :: ['albuminuria'] @entity12350 :: ('MESH:C496398', 'Chemical') :: ['sitagliptin'] @entity164 :: ('MESH:D017827', 'Disease') :: ['type'] @entity810 :: ('MESH:D058186', 'Disease') :: ['acute renal failure'] @entity23606 :: ('1990', 'Gene') :: ['elastase-1'] @entity8142 :: ('2740', 'Gene') :: ['GLP-1 receptor', 'glucagon-like peptide (GLP)-1 receptor'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']
@entity164 :: (MESH:D017827,Disease) :: ['type']
