Effects of 5 Weeks Treatment With Dapagliflozin in Type 2 Diabetes Patients on How the Hormone Insulin Acts on Sugar Uptake in Muscles.
Condition: Diabetes Mellitus, Type 2; Skeletal Muscle Insulin Sensitivity
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance; Hypersensitivity
Intervention: Dapagliflozin
Intervention description: The study consist of 5 weeks treatment period 1, 6-8 weeks wash-out period and 5 weeks treatment period 2.
The patient will be administered dapagliflozin 10 mg during Period 1 or Period 2.
Intervention MeSH terms: Dapagliflozin
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 26.0
Sex: All
Minimum age: 40 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: T2DM, insulin resistance, skeletal muscle, mitochondria, dapagliflozin

Summary:

      The purpose of this study is to investigate the effects of 5 weeks treatment with
      dapagliflozin in type 2 diabetes patients on how the hormone insulin acts on sugar uptake in
      muscles.
    

Eligibility 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.

        Exclusion Criteria:

          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.