• Forearm blood flow
  

• Insulin sensitivity, plasma volume, transcapillary escape rate, inhibition to vasodialtory response, changes in cardiac output, plasma catecholamine levels, changes in plasma hormone/markers of vascular permeability, safety and tolerability.
  

Inclusion Criteria:

• BMI 27-36 kg/m2 inclusive and at least two additional features of the metabolic syndrome or a first degree relative with a history of type 2 diabetes mellitus. BMI = Weight/height², (where weight is in kg, height in m).
• Male or female aged 30 to 65 years, inclusive, at screening.
• Female subjects must be post-menopausal (i.e. >6 months without menstrual period), surgically sterile, or using effective contraceptive measures (oral contraceptives, Norplant Depo-Provera) or intra-uterine devices (IUD) (a diaphragm with spermicide or a condom with spermicide). Women of childbearing potential must use effective contraceptive measures for at least 1 month prior to visit 1, and should continue to use the same contraceptive method during the study and for 30 days after discontinuing study treatment.
• Willing and able to provide a signed and dated written informed consent.

Exclusion Criteria:

• Subjects with type 2 diabetes mellitus defined as an HbA1c level >6.5% or a fasting plasma glucose of > 7.0 mmol/L. If fasting plasma glucose is between 6.1 and 7.0 mmol/L then a 75 g oral glucose test will be performed to exclude diabetes mellitus.
• Subjects who have initiated lipid lowering therapy within the last 6 months and subjects who have increased the dose of these therapies within the last 3 months prior to study start.
• Subjects who are taking Non Steroidal Anti-inflammatory Drugs, fibrates, anticoagulants or cardiovascular medications (β-blockers, nitrates, calcium antagonists, ACE inhibitors, angiotensin II antagonists, alpha blockers, diuretics, centrally acting anti-hypertensives, directly acting antihypertensives e.g., diazoxide, digoxin, anti-arrhythmics) and are unable to stop these medications for the duration of the study.
• Exposure to a thiazolidinedione (TZD) or other PPAR-γ agonist (e.g. rosiglitazone, troglitazone, pioglitazone, G1262570) within the last 4 months or participation in a clinical study involving a TZD or PPAR-γ agonist.
• Subjects who have required the use of any anti-diabetic medication at any time.
• Use of any investigational drug within 30 days preceding the first dose of medication at the start of the study.
• Subjects with a documented history of significant hypersensitivity (e.g. difficulty swallowing, difficulty breathing, tachycardia or skin reaction) to thiazolidinediones or PPAR-γ agonists.
• Systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg or receiving antihypertensive therapy.
• Subjects with unstable or severe angina (requiring continual therapy) or congestive heart failure.
• Presence of clinically significant hepatic disease.
• Clinically significant anaemia.
• Subjects with creatinine clearance <40 mL/min.
• Women who are lactating, pregnant or planning to become pregnant during the course of the study.
• Alcohol or drug abuse within the last 6 months.