Effects of 5 weeks treatment with dapagliflozin in type 2 diabetes patients on how the hormone insulin acts on sugar uptake in muscles. - DAPAMAAST

Exclusion Criteria

• Inclusion Critieria:
• 1. Patients are able to provide signed and dated written informed consent prior to any
• study specific procedures.
• 2. Women are post-menopausal (defined as at least 1 year post cessation of menses) and
• aged ≥ 45 and ≤ 70 years. Males are aged ≥ 40 years and ≤ 70 years. Patients should
• have suitable veins for cannulation or repeated venipuncture.
• 3. Patients are diagnosed with T2DM for at least the last 6 months.
• 4. Patients are 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 months5. HbA1c levels ≥6.0% (=42 mmol/mol) and ≤9.0% (75 mmol/mol).
• 5. Have a body mass index (BMI) ≤ 35 kg/m2.
• 1. Involvement in the planning and conduct of the study (applies to both AstraZeneca
• staff and staff at third party vendor or at the investigational sites).
• 2. Previous enrolment in the present study or participation in another clinical study with
• an investigational product during the last 3 months or as judged by the Investigator.
• 3. History of or presence of any clinically significant disease or disorder including a
• recent (< 3 months) cardiovascular event which, in the opinion of the Investigator,
• may either put the patient at risk because of participation in the study or influence the
• results or the patient’s ability to participate in the study.
• 4. Clinical diagnosis of Type 1 diabetes, maturity onset diabetes of the young,
• secondary diabetes or diabetes insipidus.
• 5. Unstable/rapidly progressing renal disease or estimated Glomerular Filtration Rate <
• 60 mL/min (Cockcroft-Gault formula).
• 6. Clinically significant out of range values of serum levels of either alanine
• aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase
• (ALP) in the Investigator’s opinion.
• 7. Contraindications to dapagliflozin according to the local label.
• 8. Use of antidiabetic drugs other than metformin within 3 months prior to screening.
• 9. Weight gain or loss > 5 kg in the last 3 months, ongoing weight-loss diet
• (hypocaloric diet) or use of weight loss agents.
• 10. History of drug abuse or alcohol abuse in the past 12 months.
• 11. Any clinically significant abnormalities in clinical chemistry, hematology or
• urinalysis or other condition the Investigator believes would interfere with the
• patient’s ability to provide informed consent, comply with study instructions, or
• which might confound the interpretation of the study results or put the patient at
• undue risk.
• 12. Plasma donation within one month of screening or any blood donation/blood loss
• > 500 mL within 3 months prior to screening or during the study.
• 13. Anemia defined as Hemoglobin (Hb) < 115 g/L (7.1 mM) in women and < 120 g/L
• (7.5 mM) in men.
• 14. Use of anti-coagulant treatment such as heparin, warfarin, platelet inhibitors,
• thrombin and factor X inhibitors.
• 15. Use of medication such as oral glucocorticoids, anti-estrogens or other medications
• that are known to markedly influence insulin sensitivity.
• 16. Use of loop diuretics.
• 17. Regular smoking and other regular nicotine use.
• 18. Any contra-indication to magnetic resonance imaging scanning. These
• contra-indications include patients with following devices:
• - Central nervous system aneurysm clip
• - Implanted neural stimulator
• - Implanted cardiac pacemaker of defibrillator
• - Cochlear implant
• - Metal containing corpora aliena in the eye or brain.
• 19. 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.