A RANDOMISED, DOUBLE-BLIND, PARALLEL GROUP, PLACEBO-CONTROLLED, MULTICENTRE STUDY TO EVALUATE THE SAFETY, TOLERABILITY AND EFFICACY OF ORAL GW677954 CAPSULES 2.5mg, 5mg, 10mg AND 20mg A DAY FOR WEEKS IN OVERWEIGHT DYSLIPIDAEMIC SUBJECTS

INTERVENTION: Product Name: GW677954 Product Code: GW677954 Pharmaceutical Form: Capsule* Current Sponsor code: GW625019 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2.5, 5, 10, 20‐ Pharmaceutical form of the placebo: Capsule* Route of administration of the placebo: Oral use CONDITION: Overweight Dyslipidaemic Subjects ; MedDRA version: 7.1 Level: LLT Classification code 10052066 PRIMARY OUTCOME: Main Objective: To compare the effect of GW677954 at doses of 2.5mg, 5mg, 10mg and 20mg with those of placebo on non‐HDL‐C at 24 weeks in overweight subjects with low HDL‐C, high TGs dyslipidaemia.; Primary end point(s): Percentage change from baseline in non‐HDL‐C based on log‐transformed data at; week 24.; Secondary Objective: To evaluate temporal changes in PD glycemic parameters,effect on fasting insulin and C‐peptide levels,and on measures of insulin resistance through homeostasis model resulting from administering a range of doses of GW677954(±metformin) in subjects with T2DM.; To investigate the effects of a range of doses of GW677954(± metformin) versus placebo(± metformin) on lipid parameters. ; To characterize the population PK of GW677954(± metformin).; To characterize the safety profile of GW677954 To investigate the effects of a range of doses of GW677954 (± metformin) versus placebo (± metformin) on biomarkers of fluid retention, cardiovascular risk, systemic inflammation, and insulin sensitivity.; To characterise the safety and tolerability of GW677954 at doses of 2.5mg, 5mg,10mg and 20mg and compare with that of placebo through assessment of physical examination, vital signs, clinical laboratory tests, ophthalmic assessments and AE reporting. INCLUSION CRITERIA: 1. Waist circumference =102cm (men) or =88cm (women) at visit 1 2. Fasting plasma HDL‐C =40mg/dL (1.03mmol/L) (men) or =50mg/dL (1.29mmol/L) (women) at Screening Visit 1 3. Fasting TGs =150mg/dL (1.69mmol/L) and =800mg/dL (8.96mmol/L) at Screening Visit 1 4. Subjects whose plasma LDL‐C concentration does not require treatment according to the NCEP ATP III guidelines at Screening Visit 1 • Plasma LDL‐C concentration =190mg/dL (=4.91mmol/L) if no more than one cardiovascular risk factor, or • Plasma LDL‐C concentration =160mg/dL (=4.13mmol/L) if two or more cardiovascular risk factors, and a 10‐year congestive heart failure (CHF) risk =10% (Framingham Point Scores), or • Plasma LDL‐C concentration =130mg/dL (=3.36mmol/L) if two or more cardiovascular risk factors, and a 10‐year CHF risk >10% and =20% (Framingham Point Scores). 5. Male and female subjects 18 to 70 years of age (inclusive at the time of Screening) at Visit 2