To Investigate the Safety, Tolerability and Pharmacodynamics of GSK2890457 in Healthy Volunteers and Subjects With Type 2 Diabetes

Inclusion Criteria:Part A (Healthy Subjects)

- Subject able to understand and voluntarily provide the consent to participate in the
study

- 18 - 70 years of age, inclusive, at the time of signing the informed consent and Body
Mass Index (BMI) between 18.0 and 35.0 Kilogram (kg) per m^2, inclusive

- Understands and is willing, able and likely to be compliant with taking study drug and
comply with all study procedures and restrictions

- Subject is willing to consume the foods that are part of the standardized breakfast,
lunch, and dinner

- In good general health with no clinically significant and relevant abnormalities of
medical history or physical examination which includes adequate renal function,
alanine transaminase (ALT), alkaline phosphatase and bilirubin <=1.5x Upper Limit of
Normal (ULN )

- QTcF < 450 millisecond (msec); or QTcF < 480msec for subjects with right Bundle Branch
Block

- Females must be post-menopausal

- Females on hormone replacement therapy (HRT) must discontinue HRT to allow
confirmation of post-menopausal status prior to study enrollment

- Females who are > 3 months postpartum and who have undergone a surgical sterilization
procedure are eligible to participate in consultation with the GSK Medical Monitor

Parts B and C (Type 2 Diabetic Subjects)

- All the criteria mentioned in Part A except Body Mass Index (BMI) should be between
30.0 and 42.0 kg per m^2

- Diagnosis of T2D for at least 3 months, as defined by the American Diabetes
Association

- All T2D subjects must meet label recommendations for metformin

- For Part B, subjects must be willing to discontinue metformin and replace it with
daily liraglutide administered by subcutaneous injection and they must meet label
recommendations

- No personal history or family history of medullary thyroid carcinoma or Multiple
Endocrine Neoplasia syndrome type 2

Exclusion Criteria:

- History of gastrointestinal disease, current or chronic history of liver disease,
history of serious, severe or unstable physical or psychiatric illness , significant
cardiovascular disease, surgery for weight loss or gastrointestinal surgery within 3
months of screening, any documented or reported eating disorder, uncontrolled
hypertension, as evidenced by systolic pressure>160 or diastolic pressure >90 mmHg

- Positive test for HIV, Hepatitis B, or Hepatitis C at Screening

- Subjects with significant ECG abnormalities

- For subjects in Part C (continuing metformin), history of untreated pernicious anemia
or who have laboratory parameters suggestive of subclinical megaloblastic anemia

- Presence of or symptoms of an active infection

- Uncorrected Thyroid Dysfunction

- History of chronic or acute pancreatitis

- Currently dieting to lose weight including, but not limited to, participation in a
program designed to alter body weight within the last 60 days and unwilling to
maintain relatively consistent exercise patterns throughout the study

- Current or recent history (within one year of screening) of alcohol or other substance
abuse

- Unable to refrain from the use of non-prescription drugs

- Current participation in another clinical study or participation in a clinical study
involving an investigational drug within 30 days of the screening visit

- History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy

- An employee of the sponsor or the study site or members of their immediate family.