Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2330672 in Type 2 Diabetes Patients Taking Metformin

Inclusion Criteria

• Males and females aged between 30 and 64 years of age inclusive, at the time of signing the informed consent.
• Subjects with documented T2DM diagnosis (diagnosed not less than 3 months prior to screening); AND one of the following: taking stable metformin 850 milligrams (mg) twice daily (BID) (or the equivalent of 1700 mg/day) for at least 4 weeks prior to screening and a glycosolated haemoglobin A1c (HbA1c) of >=7.0% to =1000 mg/day to =7.5% to 1700 to =7.0% to =60 milliliters (mL)/minute (min); No conditions which make hypoxia, dehydration, or sepsis likely; No clinical or laboratory evidence of hepatic disease (including history of cholecystitis or symptomatic gallstones) and cardiac disease (including a history of myocardial infarction or heart failure). Subjects with a history of cholelithiasis and uncomplicated cholecystectomy more than 3 months before screening may be eligible if approved by the GlaxoSmithKline (GSK) Medical Monitor; No excessive alcohol intake.
• C-peptide of >0.8 nanogram (ng)/mL at screening visit.
• Urine albumin-to-creatinine ratio 40 milli international units (MIU)/mL and estradiol 160 or diastolic pressure >90. Subjects taking anti-hypertensive medications are permitted.
• Significant ECG abnormalities, defined as follows: Heart rate (resting) 100 beats per minute (bpm); PR Interval 220 milliseconds (msec); QRS duration 120 msec
• History of untreated pernicious anemia or who have laboratory parameters suggestive of subclinical megaloblastic anemia (e.g., increased mean corpuscular volume with low red blood cells count and/or haemoglobin level).
• Current or relevant previous significant medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that, in the opinion of the investigator, presents undue risk from the study medication or procedures.
• Thyroid Disease: Uncorrected Thyroid Dysfunction: Fasting plasma thyroid stimulating hormone (TSH) outside of the normal range, as determined at the screening visit; Subjects on stable thyroid replacement therapy and with TSH in the normal range are eligible if approved by the GSK Medical Monitor; Unevaluated thyroid nodule or goiter at Screening.
• History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation
• CRITERIA BASED UPON DIAGNOSTIC ASSESSMENTS:
• Alanine transaminase, alkaline phosphatase and bilirubin > 1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin =450 msec; or QTcF >=480 msec in subjects with Bundle Branch Block (subjects with left bundle branch block are excluded)
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• A positive test for human immunodeficiency virus antibody
• A positive pre-study drug/alcohol urine screen
• A subject with a positive urine cotinine test result will be excluded from the study unless in the judgment of the Investigator the subject will be able to abstain from using tobacco for the duration of the in-house periods of the study.
• OTHER CRITERIA
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 da