Study to investigate mitochondrial function and insulin sensitivity in skeletal muscle in subjects with T2DM.
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Provision of signed and dated, written informed consent prior to any study specific procedures • Post-menopausal females aged between = 45 and = 70 years and/or males aged between = 40 years and = 70 years. Patients should have suitable veins for cannulation or repeated venipuncture. • Patients diagnosed with T2DM for at least the last 6 months, based on American Diabetes Association 2016 standards. • Patients on no other anti-diabetic drug treatment, or on stable maximum 3000 mg daily dose metformin treatment and/or on stable dose of a DPPIV inhibitor treatment for at least the last 3 months • HbA1c levels =6.0% (=42 mmol/mol) and =9.0% (75 mmol/mol) • Body mass index (BMI) = 38 kg/m2 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 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: • Any of clinically significant disease or disorder including a recent cardiovascular event • Diagnosis of Type 1 Diabetes Mellitus, maturity onset diabetes of the young, secondary diabetes or diabetes insipidus • Unstable/rapidly progressing renal disease or estimated Glomerular Filtration Rate < 60 mL/min (Cockcroft-Gault formula) • History of drug abuse or alcohol abuse in the past 12 months • Any clinically significant abnormalities in clinical chemistry, hematology or urinalysis • Contraindications to dapagliflozin according to the local label • Anemia defined as Hemoglobin (Hb) < 115 g/L (7.1 mM) in women and < 120 g/L (7.5 mM) in men. • Use of anti-coagulant treatment • Use of medication such as oral glucocorticoids, anti-estrogens or other medications that are known to markedly influence insulin sensitivity • Use of loop diuretics • Regular smoking /nicotine use • Any contra-indication to magnetic resonance imaging scanning • Patients, who do not want to be informed about unexpected medical findings, or do not wish that their physician be informed about coincidental findings, cannot participate in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate if dapagliflozin improves skeletal muscle insulin sensitivity expressed as corrected glucose disposal rate (cGDR) in comparison with placebo after 5-week double blind treatment. Insulin sensitivity will be determined using a 2-step euglycemic hyperinsulinemic clamp (EHC) procedure.;Secondary Objective: Not applicable.;Primary end point(s): Comparison of dapagliflozin versus placebo after 5 weeks treatment in skeletal muscle insulin sensitivity measured as cGDR using a 2-step EHC procedure.;Timepoint(s) of evaluation of this end point: 18-20 week | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): No secondary end points.;Timepoint(s) of evaluation of this end point: No secondary end points. | — |
Countries
Netherlands
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed