A Study to Determine the Safety and Efficacy of Albiglutide Administered in Combination With Insulin Glargine

This randomized, open-label, active-controlled, parallel-group, multicenter study evaluates the safety and efficacy of a weekly subcutaneously injected dose of albiglutide in combination with insulin glargine as compared with the combination of insulin glargine and preprandial lispro insulin in subjects with type 2 diabetes. Subjects with a historical diagnosis of type 2 diabetes who are inadequately controlled despite the use of insulin glargine or other intermediate- or long-acting insulins for >/= 6 months but < 5 years, with or without oral antidiabetic medications, who are unable to achieve a glycosylated hemoglobin value of < 7% will be recruited into the study. Subjects must also be willing and capable of pursuing an intensive regimen of both basal and preprandial insulin.

Inclusion criteria

• Subjects with type 2 diabetes, currently treated with insulin glargine or other intermediate- or long-acting insulin, with or without oral antidiabetic medications, but experiencing inadequate glycemic control and willing and capable of participating in a regimen of intensive insulin administration. A subject who has been on an intermediate- or long acting insulin for >/=6 months but <5 years, and, in spite of dosage adjustments based on home blood glucose monitoring, is unable to achieve a HbA1c of <7%.
• BMI >/= 20kg/m2 and </=45 kg/m2
• Fasting C-peptide >/=0.8 ng/mL (>/= 0.26 nmol/L)
• HbA1c between 7.0% and 10.5%, inclusive
• Use of oral or systemically injected glucocorticoids is generally not allowed within 3 months before randomization; inhaled, intra articular, and topical corticosteroids are allowed
• Hemoglobin </=11 g/dL for male subjects and >/=10 g/dL for female subjects
• Creatinine clearance >60 mL/min (calculated using the Cockcroft Gault formula)
• Thyroid stimulating hormone level is normal or clinically euthyroid as demonstrated by further thyroid tests (e.g., T4, T3, thyroid-binding globulin)
• Female subjects of childbearing potential (i.e., not surgically sterile and/or not postmenopausal) must be practicing adequate contraception. Adequate contraception must be practiced for the duration of participation in the study including the 8 week Posttreatment Follow-up Period
• Able and willing to monitor his or her own blood glucose concentrations with a home glucose monitor as per the protocol recommendations of self administration
• No major illness or debility that in the investigator's opinion prohibits the subject from actively participating in their diabetes management and completing the study
• Able and willing to provide written informed consent

Exclusion criteria

• History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 3 years before Screening.
• History of treated diabetic gastroparesis
• Current ongoing symptomatic biliary disease or history of pancreatitis
• History of significant gastrointestinal surgery, including gastric bypass and banding, antrectomy, Roux en Y bypass, gastric vagotomy, small bowel resection, or surgeries thought to significantly affect upper gastrointestinal function
• Recent clinically significant cardiovascular and/or cerebrovascular disease including but not limited to the following:

• Previous history of stroke or transient ischemic attack within 1 month before Screening.
• Acute coronary syndrome, which includes the following:
• Documented MI within the 2 months before Screening and during the period up until receiving the first dose of study medication
• Any cardiac surgery including percutaneous transluminal coronary angioplasty, coronary stent placement, or coronary artery bypass graft surgery within the 2 months before Screening and during the period up until receiving the first dose of study medication
• Unstable angina not responsive to nitroglycerin within the 2 months before Screening and during the period up until receiving the first dose of study medication
• Unstable cardiac rhythm, however, as an example, controlled atrial fibrillation is allowed
• Current or history of heart failure (New York Heart Association class I to IV).
• Resting systolic pressure is >160 mm Hg and/or diastolic pressure >100 mm Hg.
• QTc interval (Fridericia) >470 ms confirmed by a central reader at Screening
• History of stroke or other central nervous system disorder that would negatively impact the subject's ability to participate in a program of intensive insulin management (eg, physically or mentally incapable of performing home blood glucose monitoring or administering and/or adjusting insulin dosage)
• Hemoglobinopathy that may affect determination of HbA1c
• History of human immunodeficiency virus infection
• History of total bilirubin >1.5 × ULN unless the subject has a previously known history of Gilbert's syndrome and a fractionated bilirubin that shows conjugated bilirubin <35% of total bilirubin
• ALT or aspartate aminotransferase (AST) >2.5 ×ULN
• Fasting triglyceride level >850 mg/dL at Screening or Week -1 (Visit 5).
• Acute symptomatic (within 3 months before Screening) infection with hepatitis B or hepatitis C; however, subjects with past or chronic hepatitis B or hepatitis C are allowed provided the requirements for ALT, AST, and total bilirubin are met
• History of a psychiatric disorder that will affect the subject's ability to participate in the study
• History of alcohol or substance abuse within 1 year before Screening
• Positive urine drug screen at Screening, unless the subject is taking a medically approved medication for which a positive drug screen simply verifies the use of this medication
• Hypoglycemia unawareness which has impaired cognitive function and required outside assistance
• Female subject is pregnant (confirmed by laboratory testing), lactating, or <6 weeks postpartum
• Known allergy to any GLP 1 analogue, insulin, other study medications' excipients, excipients of albiglutide, or Baker's yeast
• Receipt of any investigational drug within the 30 days, or 5 half lives whichever is longer, before Screening or a history of receipt of an investigational antidiabetic drug within the 3 months before randomization, or receipt of albiglutide in previous studies
• Current use of any GLP 1 analogue
• History of type 1 diabetes mellitus, diabetic complications (e.g., active proliferative retinopathy or severe diabetic neuropathy) that in the opinion of the investigator would preclude effective participation in the study, or a history of ketoacidosis or hyperosmolar coma
• Contraindications (as per the prescribing information) for the use of either background or potential randomized study medications (e.g., insulin glargine or lispro insulin)
• History or family history of medullary carcinoma
• History or family history of multiple endocrine neoplasia type 2