A phase 4, monocenter, randomized, double-blind, comparator-controlled, parallel-group, mechanistic intervention trial to assess the effect of 8-week treatment with the dipeptidyl peptidase-4 inhibitor (DPP-4i) linagliptin versus the sulfonylurea (SU) derivative glimepiride on renal physiology and biomarkers in metformin-treated patients with type 2 diabetes mellitus (T2DM)
- Conditions
- Type 2 Diabetes Mellitus1001842410029149
- Registration Number
- NL-OMON41714
- Lead Sponsor
- Vrije Universiteit Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 48
* Caucasian
* Male and Female (must be post-menopausal; no menses >1 year)
* Age: 35 - 75 years
* BMI: >25 kg/m2
* Type 2 diabetes mellitus (HbA1c: 6.5 - 9% DCCT or 48 - 75 mmol/mol IFCC) who are being treated with a stable dose of oral antihyperglycemic agents (metformin monotherapy or combination of metformin and low dose SU derivative) for at least 3 months prior to inclusion
* All patients with previously diagnosed hypertension should use a RAS-interfering agent (ACE-i / ARB) for at least 3 months
* Current / chronic use of the following medication: thiazolidinediones, insulin, glucocorticoids, immune suppressants, antimicrobial agents or chemotherapeutics. Subjects on diuretics will only be excluded when these drugs (e.g. hydrochlorothiazide) cannot be stopped for the duration of the study
* Chronic use of NSAIDS will not be allowed, unless used as incidental medication (1-2 tablets) for non-chronic indications (i.e. sports injury, head-ache or back ache). However, no such drugs can be taken within a time-frame of 2 weeks prior to renal-testing
* Estimated Glomerular Filtration Rate <60 mL/min/1.73m2 (determined by the Modification of Diet in Renal Disease (MDRD) study equation)
* Pregnancy
* Frequent occurrence of (confirmed) hypoglycemia (plasma glucose *3.9 mmol/L)
* Current urinary tract infection and active nephritis
* Recent (<6 months) history of cardiovascular disease, including: acute coronary syndrome, chronic heart failure (New York Heart Association grade II-IV), stroke, transient ischemic neurologic disorder
* Complaints compatible with or established gastroparesis
* Active liver disease or a 3-fold elevation of liver enzymes (aspartate aminotransferase (AST) / alanine aminotransferase (ALT)) at screening
* History of or actual pancreatic disease
* History of or actual malignancy (except for basal cell carcinoma)
* History of or actual severe mental disease
* Substance abuse (alcohol: defined as >4 units/day)
* Allergy to any of the agents used in the study
* Individuals who are investigator site personnel, directly affiliated with the study, or are immediate (spouse, parent, child, or sibling, whether biological or legally adopted) family of investigator site personnel directly affiliated with the study
* Inability to understand the study protocol or give informed consent
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Renal hemodynamics, measured as:<br /><br>* Glomerular filtration rate (GFR; measured by the inulin-clearance technique)<br /><br>* Effective renal plasma flow (ERPF; measured by the para-aminohippuric acid<br /><br>(PAH) clearance technique)</p><br>
- Secondary Outcome Measures
Name Time Method <p>To assess changes from baseline following 8-week treatment with a DPP-4i versus<br /><br>SU derivative on:<br /><br>* Systolic and diastolic blood pressure, mean arterial pressure<br /><br>* Heart rate<br /><br>* Renal tubular function, measured as:<br /><br>o Fractional sodium- and urea excretion<br /><br>o Urine osmolality<br /><br>* Renal damage, measured by urine biomarkers as:<br /><br>o Albumin/creatinine-ratio (Glomerular)<br /><br>o NGAL and KIM*1 (Tubular)<br /><br><br /><br>Exploratory Objectives<br /><br>* Resting heart rate variability<br /><br>* Cardiac autonomic nervous system function<br /><br>* Systemic hemodynamic variables<br /><br>* Microvascular function<br /><br>* Arterial stiffness<br /><br>* Glycemic variables<br /><br>* Lipid spectrum<br /><br>* Biomarkers<br /><br>* Plasma DPP4- and ACE activity<br /><br>* Body anthropometrics<br /><br>* Body fat content</p><br>