Intervention: Dapagliflozin
Trial phase: Phase 4
ATC code: A10BD15 | A10BD21 | A10BD25 | A10BK01
SMILES: CCOc1ccc(Cc2cc([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)ccc2Cl)cc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 17
Group description: Dapagliflozin 5 mg daily by mouth for 2 weeks followed by 10 mg by mouth daily for 10 weeks

Dapagliflozin: Patients with Type 2 diabetes will be randomized to receive dapagliflozin 5 mg daily for 2 weeks followed by10 mg daily for 10 weeks by mouth or matching placebo for 12 weeks. All subjects will receive measurements of fasting plasma glucose, Free Fatty Acids, inflammatory markers and adipocytokines, monocyte inflammation, as well as ultrasound assessment of flow-mediated dilatation (FMD) of the brachial artery at baseline and after 12 weeks of drug treatment with either dapagliflozin or placebo.
Eligibility criteria:
Inclusion Criteria:

Provision of informed consent prior to any study specific procedures

Men and women, ages 21 to 70 years. i) Women of childbearing potential must be using an acceptable method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized.

ii) Women must not be pregnant or breastfeeding.

Patients with Type 2 Diabetes Mellitus with the following parameters at study entry: hemoglobin A1c ranging from 7.0% to 9.0% and a fasting blood glucose less than or equal to 200 mg/dL.
Patients must be on a stable dose of Metformin therapy for 3 months; the dose of metformin will not change for the duration of the study.
Patients are allowed, but not required, to be on statins, Angiotensin Converting Enzyme (ACE) inhibitors, and angiotensin-receptor blockers at doses that have been stable for at least the last 3 months prior to enrollment in the study. Doses will not be changed for the duration of the study.
Patients must have a Body Mass Index between 27-35 kg/m2
Patients must have a stable body weight for three months prior to enrollment in the study.
Patients must have a Creatinine Clearance greater than 60 mL/min (calculated by Cockcroft-Gault formula).
Patients must have Hematocrit greater than or equal to 34%; Serum creatinine less than1.5 mg/dl in men and 1.4 mg/dl in women and Creatinine Clearance greater than 60 ml/min; and serum aspartate aminotransferase (AST) less than 2.5 times upper limit of normal, serum alanine transaminase (ALT) less than 2.5 times upper limit of normal, serum alkaline phosphatase less than 2.5 times upper limit of normal.

Exclusion Criteria:

History of Type 1 diabetes mellitus
Women who are pregnant or breastfeeding
Patients receiving lipid-lowering medications other than statins within the last 3 months.
Patient receiving SGLT-2 inhibitors, incretin therapy, dipeptidyl peptidase 4 (DPP-4) inhibitors, thiazolidinediones, insulin, sulfonylureas, alpha-glucosidase inhibitors, corticosteroids, immunosuppressive therapy, thiazide or loop diuretics, or hormone replacement therapy within the last 3 months .
Patient must stop treatment with nonsteroidal anti-inflammatory drugs (NSAID) and antioxidant vitamin supplements at least one week prior to the start of the study
Patients with diabetic gastroparesis.
Patients with current tobacco use.
Patients with active malignancy.
Patients with history of urinary bladder cancer
Patients with a history of clinically significant heart disease, peripheral vascular disease, or pulmonary disease will not be studied
Subjects with a history of any serious hypersensitivity reaction to dapagliflozin.
Prisoners, or subjects who are involuntarily incarcerated.
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Patients with significant cardiac,hepatic or renal disease (Creatinine Clearance less than 60 mL/min calculated by Cockcroft-Gault formula) will be excluded.