Type 2 Diabetes Mellitus MedDRA version: 20.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861
Conditions
Interventions
Trade Name: Ozempic
Pharmaceutical Form:
INN or Proposed INN: Semaglutide
CAS Number: 910463-68-2
Other descriptive name: SEMAGLUTIDE
Concentration unit: mg milligram(s)
Concentration type: range
Co
Sponsors
Aarhus University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Diagnose of type 2 diabetes. HbA1c level of 7% (53 mmol/mol) or more. Age of 50 years or more with established cardiovascular disease (prior myocardial infarction, prior stroke or prior transient ischemic attack, prior coronary, carotid or peripheral arterial revascularization, more than 50 % stenosis on angiography or imaging of coronary, carotid or lower extremities arteries, history of symptomatic coronary heart disease documented by e.g. positive exercise stress test or any cardiac imaging or unstable angina with electrocardiography (ECG) changes), or chronic heart failure (New York Heart Association class II or III). or Age of 60 years or more with at least one cardiovascular risk factor (persistent microalbuminuria (30-299 mg/g) or proteinuria, hypertension and left ventricular hypertrophy by electrogram or imaging, left ventricular systolic or diastolic dysfunction by imaging or ankle/brachial index less than 0.9). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: Estimated glomerular filtration rate < 60 ml/min. Treatment with a SGLT2-inhibitor, GLP-1-receptor agonist or dipeptidyl-peptidase 4 inhibitor within 30 days before screening or insulin other than basal or premixed within 30 days before screening. A history of an acute coronary or cerebrovascular event within 90 days before randomization. Planned revascularization of a coronary, carotid, or peripheral artery. Inability to give informed consent. Active cancer diagnosis other than basal cell carcinoma. Indication of liver disease (serum ALAT, ASAT or alkaline phosphatase above 3 x upper limit). Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption. Treatment with systemic steroids at time of randomization. Change in dosage of thyroid hormones within 6 weeks prior to screening. Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance with study procedures or study drug intake. Chronic or acute pancreatitis. Pregnancy or breastfeeding. Allergy to either empagliflozin or semaglutide or any of the excipients contained in the drugs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The study has two co-primary aims: Aim 1: To test the hypothesis that treatment with empagliflozin, semaglutide or the combination vs. placebo improves arterial function in T2DM patients. Further, we aim to compare the different treatment modalities with each other (empagliflozin vs semaglutide, combination vs semaglutide, combination vs empagliflozin). The main outcome is change in arterial stiffness assessed as carotid-femoral PWV. Aim 2: To test the hypothesis that treatment with empagliflozin, semaglutide or the combination vs. placebo improves renal oxygenation in T2DM patients. Further, we aim to compare the different treatment modalities with each other (empagliflozin vs semaglutide, combination vs semaglutide, combination vs empagliflozin). The main outcome is change in renal oxygenation assesed by magnetic resonance imaging (MRI). ;Secondary Objective: Aim 3: To test the hypothesis that treatment with empagliflozin, semaglutide or the combination vs. placebo improves platelet function in T2DM patients. Further, we aim to compare the different treatment modalities with each other (empagliflozin vs semaglutide, combination vs semaglutide, combination vs empagliflozin). Aim 4: To test the hypothesis that treatment with empagliflozin, semaglutide or the combination vs. placebo improves glycemic control in T2DM patients. Further, we aim to compare the different treatment modalities with each other (empagliflozin vs semaglutide, combination vs semaglutide, combination vs empagliflozin). Aim 5: To test the effect of empagliflozin, semaglutide or the combination vs. Placebo on retinal metabolism and flow. Further, we aim to compare the different treatment modalities with each other (empagliflozin vs semaglutide, combination vs semaglutide, combination vs empagliflozin). ;Primary end point(s): The primary endpoint is change in arterial stiffness assessed as carotid-femoral PWV and change in renal oxygenation assesed by magnetic resonance i | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints to Aim 1: Change in endothelial function, ambulatory PWV and central Blood Pressure indices and ambulatory Blood Pressure. Secondary endpoints to Aim 2: Change in glomerular filtration rate (GFR), renal plasma flow (RPF), corticomedullary sodium homeostasis and markers of the renin-angiotensin system. Change in urinary albumin excretion and urine-Prostaglandin E (PGE) Secondary endpoints to Aim 3: Change in platelet aggregation, Platelet count and turnover Secondary endpoints to Aim 4: Change in mean glucose level and glucose variability assessed by continuous glucose monitoring (CGM) and HbA1c. Change in Insulin sensitivity, beta-cell responsitivity and hepatic insulin extraction evaluated by the oral minimal model method using an oral glucose tolerance test with multiple bloodsampling. Change in Betahydroxybutyrat levels. Secondary endpoints to Aim 5: Change in retinal oxygenation, metabolism and flow assed by oximetry and retinal arterial and venolar vasomotion assessed by Retinal Vessel Analyzer (RVA). Change in retinal thickness assessed by Optical Coherence Tomography (OCT) ;Timepoint(s) of evaluation of this end point: Endpoints will be evaluated at baseline, after 16 weeks of treatment and after 32 weeks of treatments. | — |
Countries
Denmark
Contacts
Public ContactEsben Laugesen
Aarhus University Hospital
Outcome results
None listed