typé 2 diabetes
Conditions
Sponsors
Sten Madsbad
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Elegible for inclusion are male patients aged =18 years with T2DM who are either drug naïve (no anti-diabetes agents for =12 weeks prior to randomization) with HbA1c =10.0% or taking any background anti-diabetes therapy (except insulin) with HbA1c =9.0% despite diet and exercise counseling. 6.1 INCLUSION CRITERIA: • Age = 18 years • BMI = 28 kg/m2 • HbA1c = 9.0% (=10% in diet or metformin only treated patients) • Fasting C-peptide = 500 pmol/L • Unchanged antiglycemic treatment 12 weeks prior to inclusion as assessed by investigator 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 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: EXCLUSION CRITERIA: • Insulin treatment within 3 months of informed consent • Type 1 diabetes • Psychiatric disorder or mental retardation • Drug or alcohol abuse within 3 months from informed consent • Poor compliance • Anemia (hgb = 6.4 mmol/L) or other blood dyscrasias causing hemolysis or unstable red blood cells • Indication of liver disease, defined by serum levels of alanine amininotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit • Impaired renal function (eGFR 100 at rest) o Known bladder atony o Cardia insufficiency or non-congenital pylorus stenosis – verified endoscopically o Known gastroparesis • Allergy towards any of the drugs or diagnostics used in the protocol (insulin, empagliflozin, acipimox, glycopyrrolate, adenosine, gadolinium contrast enhancer). • Any condition which in the opinion of the investigator may jeopardize subject safety or compliance with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: We hypothesize that hyperinsulinemia and hyperglycemia are factors that may negatively influence cardiac function, while an increased availability off free fatty acids are important for maintaining cardiac function in patients with type 2 diabetes. If so the metabolic phenotype of type 2 diabetes may be a necessary adaptation for optimal cardiac function in a hyperinsulinemic and hyperglycemic environment and thus treating hyperglycemia in an insulin independent manner that does not suppress lipid oxidation could improve myocardial function and protect the heart when stressed. The aim of the present study is to elucidate the physiological importance of hyperglycemia, hyperinsulinemia and elevated free fatty acids for myocardial function during rest and chronotropic stress in patients with type 2 diabetes. ;Secondary Objective: Secondarily, the study aims to characterize metabolic effects of insulin dependent and independent glucose lowering in patients with type 2 diabetes.;Primary end point(s): PRIMARY ENDPOINT: Myocardial diastolic function (Cardiac MRI): Change in left ventricular peak filling rate (?LVPFR) Change is defined as LVPFRtreatment - LVPFRbaseline. Baseline is defined as the visit during the wash-out period preceding the treatment period. Thus, if the patient is randomized to insulin first. Baseline for insulin treatment is visit 1, and baseline for empagliflozin treatment is visit 3. ;Timepoint(s) of evaluation of this end point: The study is a 20-week prospective, interventional, comparator controlled, open label, 2-arm cross-over study where subjects are randomized to NPH insulin or Empagliflozin (25 mg once daily) treatment first for 5 weeks, followed by 3 weeks wash-out and cross-over to 5 weeks treatment with the remaining study drug. For 7 weeks preceding randomization but after inclusion, patients undergo a program of washout of pre-existing antiglycemic treatment (except metformin) and run-in of empagliflozin (see below). At | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 2.4.2 KEY SECONDARY ENDPOINT: Myocardial diastolic function: Change in left atrial passive emptying fraction 2.4.3 SECONDARY ENDPOINTS: Myocardial systolic function (Cardiac MRI): Change in left ventricular ejection fraction (?LVEF) The study design does not allow for blinding, but evaluation of primary and secondary outcomes will be performed by specialists in the field of MRI blinded to the treatment og the patients. 2.4.4 DESCRIPTIVE ENDPOINTS: CARDIOVASCULAR ENDPOINTS: a) VO2max – estimated from Aastrands two-point test. b) Change in central blood volume and hematocrite. METABOLIC ENDPOINTS: a) Basal and postprandial AUC FFA and glycerol turnover b) Endogenous glucose production and tissue glucose disposal (metabolic clearance of glucose) c) Fasting and postprandial energy expenditure and respiratory quotient. d) Glucagon/insulin ratio e) Insulin sensitivity (Average glucose metabolic clearance rate during OGTT/average insulin concentration) f) Beta-cell function (prehepatic insulin secretion rate (determined by deconvolution of C-peptide data) correlated to ambient glucose concentrations, glucose sensitivity). g) Adlibitum food intake;Timepoint(s) of evaluation of this end point: See E.5.1.1 | — |
Countries
Denmark
Contacts
Public ContactNils Bruun Joergensen
Nils Bruun Joergensen
Outcome results
None listed