Type 2 Diabetes Mellitus
Conditions
Interventions
Trade Name: Forxiga
Product Name: Dapagliflozin
Pharmaceutical Form: Film-coated tablet
Trade Name: Diamicron 30
Product Name: Diamicron 30
Pharmaceutical Form: Coated tablet
Sponsors
VU University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria • Caucasian* • Both genders (females must be post-menopausal; no menses >1 year; in case of doubt, Follicle-Stimulating Hormone (FSH) will be determined with cut-off defined as >31 U/L) • Age: 35 - 75 years • BMI: >25 kg/m2 • HbA1c: 6.5 – 9.0% Diabetes Control and Complications Trial (DCCT) or 48 - 86 mmol/mol International Federation of Clinical Chemistry (IFCC) • Treatment with a stable dose of oral antihyperglycemic agents for at least 3 months prior to inclusion • Metformin monotherapy • Combination of metformin and low dose SU derivative** • Hypertension should be controlled, i.e. =140/90 mmHg, and treated with an ACE-I or ARB (unless prevented by side effect) for at least 3 months. • Albuminuria should be treated with a RAAS-interfering agent (ACE-I or ARB) for at least 3 months. • Written informed consent * In order to increase homogeneity ** In order to accelerate inclusion, patients using combined metformin/SU derivative will be considered. In these patients, a 12 week wash-out period of the SU derivative will be observed, only when combined use has led to a HbA1c =65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
Exclusion criteria: Exclusion criteria • History of unstable or rapidly progressing renal disease • Estimated GFR 3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN • (Unstable) thyroid disease; defined as fT4 outside of laboratory reference values or change in treatment within 3 months prior to screening visit • History of or actual malignancy (except 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effects of 12-week treatment with the SGLT-2 inhibitor dapagliflozin (10 mg QD) versus the SU gliclazide (30 mg QD) on renal hemodynamics in metformin-treated T2DM patients;Secondary Objective: To investigate the effects of 12-week treatment with the SGLT-2 inhibitor dapagliflozin (10 mg QD) versus the SU gliclazide (30 mg QD) on: Secondary objectives: -Renal Tubular Function -Renal damage -Blood Pressure and heart rate -Body anthropometrics and Body fat content -Glycemic variables, Lipid spectrum, Inflammation, Biochemistry and Hematology -Microvascular function -Arterial stiffness (PWA) -Systemic hemodynamics -CANS function Exploratory objectives: -Biomarkers and gut microbiome -DNA -Insulin sensitivity -Beta-cell function ;Primary end point(s): • GFR (measured by the inulin-clearance technique) • Effective renal plasma flow (ERPF; measured by the para-aminohippurate acid (PAH) clearance technique);Timepoint(s) of evaluation of this end point: At baseline and after 12 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Baseline and after 12 weeks of treatment;Secondary end point(s): • Renal tubular function, measured as: -24-h urine sodium-, potassium-, chloride-, calcium-, magnesium-, phosphate-, urea and glucose • Renal damage, measured by urine biomarkers as: -UAE (Glomerular) -Neutrophil gelatinase-associated lipocalin (NGAL) and Kidney injury molecule-1 (KIM-1) (Tubular) • Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) (measured by oscillometric blood pressure device) • Heart rate (measured by oscillometric blood pressure device) • Body anthropometrics: waist circumference, height, body weight and body mass index (BMI) (using the formula: weight (in kg) / height2 (in m)), measured by a tape measure and calibrated weighing scale respectively • Body fat content, measured by bio-impedance analysis (BIA) • Marker of inflammation: high sensitivity C-reactive protein (hs-CRP) • Glycemic variables: Glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) • Lipid spectrum (triglycerides (TG), total-cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and free fatty acids (FFA)) • Microvascular function, measured by capillary videomicroscopy and Laser Doppler techniques • Arterial stiffness (Pulse Wave Analysis), measured by applanation tonometry • Systemic hemodynamic variables (SBP, DBP, MAP, heart rate (HR), stroke volume (SV), cardiac output (CO)/-index (CI), and total systemic vascular resistance (TPR)) derived from non-invasive beat-to-beat finger blood pressure measurements • Cardiac autonomic nervous system (CANS) function, as derived from electrocardiographic (ECG) and non-invasive beat-to-beat finger blood pressure measurements (NexFin®) measured as: -Heart rate variability (HRV); Cardiovascular autonomic reflex tests (CARTs) Exploratory end points: • Complementary markers of renal function/damage (plasma cystatin C, fibro | — |
Countries
Netherlands
Contacts
Public ContactDaniel van Raalte
VU University Medical Center
Outcome results
None listed