Type 2 Diabetes
Conditions
Keywords
Type 2 diabetes mellitus, Diabetic kidney disease, Diabetic nephropathy, Renoprotection, DPP-4 inhibitors, Linagliptin, SU derivatives, Glimepiride
Brief summary
The aim of this study is to detail the (mechanisms underlying the) actions of the DPP-4 inhibitor linagliptin on the renal system in patients with type 2 diabetes mellitus.
Detailed description
Based on preclinical and small-sized studies in non-diabetic individuals, incretin-based therapies, i.e. glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase-4 inhibitors (DPP-4i), may hold promise in preventing the onset and progression of diabetic kidney disease. However, the potential renoprotective effects of these agents, that are believed to be effectuated beyond glucose control, have not been sufficiently detailed in human diabetes. Therefore, the present study aims to explore the mechanistic and clinical effects of DPP-4i on fasting and postprandial renal physiology and biomarkers in patients with type 2 diabetes. Forty-eight patients with type 2 diabetes will undergo an eight week intervention with linagliptin or glimepiride in order to assess changes in the outcome parameters.
Interventions
DRUGLinagliptin 5 mg QD (N=24)
Linagliptin 5 mg will be taken orally, once daily for 8 weeks
DRUGGlimepiride 1 mg QD (N=24)
Glimepiride 1 mg will be taken orally, once daily for 8 weeks
Sponsors
Amsterdam UMC, location VUmc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with type 2 diabetes (HbA1c: 6.5-9.0% DCCT or 48-75 mmol/mol IFCC) * Metformin monotherapy; using a stable dose for at least 3 months prior to inclusion * Both genders (females must be post-menopausal) * Caucasian * Age: 35-75 years * Body Mass Index: \>25 kg/m2 * All patients with previously diagnosed hypertension should use a RAS-interfering agent (angiotensin converting enzyme inhibitor/angiotensin II receptor blocker) for at least 3 months
Exclusion criteria
* 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. However, no such drugs can be taken within a time-frame of 2 weeks prior to renal-testing * Pregnancy * Frequent occurrence of (confirmed) hypoglycemia (plasma glucose \<3.9 mmol/L) * Estimated Glomerular Filtration Rate \< 60 mL/min/1.73m2 (determined by the Modification of Diet in Renal Disease (MDRD) study equation) * 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 and/or neurogenic bladder * Active liver disease * 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; smoking/nicotine: defined as daily smoking/use) * Allergy to any of the agents used in the study * Inability to understand the study protocol or give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes from baseline following 8-week treatment with linagliptin vs glimepiride on fasting and postprandial renal hemodynamics, measured as GFR / ERPF (determined by inulin/para-aminohippuric-acid clearance) | 8 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Renal tubular function | 8 weeks |
| Renal damage, measured by urine biomarkers | 8 weeks |
| Blood Pressure and Heart Rate | 8 weeks |
Other
| Measure | Time frame | Description |
|---|---|---|
| Body anthropometrics: body weight, height, body mass index, waist circumference | 8 weeks | — |
| Body fat content | 8 weeks | — |
| Arterial stiffness | 8 weeks | — |
| Cardiac autonomic nervous system function | 8 weeks | — |
| Microvascular function | 8 weeks | — |
| Systemic hemodynamic variables (blood pressure, heart rate, stroke volume, cardiac output/-index, total systemic vascular resistance) | 8 weeks | Derived from non-invasive beat-to-beat finger blood pressure measurements |
| Glycemic variables | 8 weeks | Glycated hemoglobin (HbA1c) and fasting glucose |
| Lipid spectrum | 8 weeks | — |
| DPP4- and ACE activity | 8 weeks | — |
Countries
Netherlands
Outcome results
None listed