Effect of AC2993 Compared With Insulin Glargine in Patients With Type 2 Diabetes Also Using Combination Therapy With Sulfonylurea and Metformin

This is a multicenter, comparator-controlled, open-label, randomized, two-arm, parallel trial.

• Heine RJ, Van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG; GWAA Study Group. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2005 Oct 18;143(8):559-69. Summary for patients in: Ann Intern Med. 2005 Oct 18;143(8):I30.
• Pencek R, Blickensderfer A, Li Y, Brunell SC, Anderson PW. Exenatide twice daily: analysis of effectiveness and safety data stratified by age, sex, race, duration of diabetes, and body mass index. Postgrad Med. 2012 Jul;124(4):21-32. doi: 10.3810/pgm.2012.07.2567.
• Fineman MS, Mace KF, Diamant M, Darsow T, Cirincione BB, Booker Porter TK, Kinninger LA, Trautmann ME. Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment. Diabetes Obes Metab. 2012 Jun;14(6):546-54. doi: 10.1111/j.1463-1326.2012.01561.x. Epub 2012 Feb 10.

Inclusion Criteria:

• Patients have been treated with a stable dose of one of the following for at least 3 months prior to screening: 1. 1500 to 2550 mg/day immediate-release metformin (or 1500 to 2000 mg/day extended-release metformin) and at least an optimally effective dose of a sulfonylurea, or 2. a fixed-dose sulfonylurea/metformin combination therapy with the same sulfonylurea and metformin requirements as for the individual components.
• HbA1c between 7.0% and 10.0%, inclusive.
• History of stable body weight (not varying by >10% for at least three months prior to screening).
• Female patients are not breastfeeding, and female patients of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopause)

Exclusion Criteria:

• Patients are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affilated with the study.
• Patients are employed by Lilly or Amylin.
• Patients have participated in this study previously or any other study using AC2993 or GLP-1 analogs.
• Patients have participated in an interventional medical, surgical, or pharmaceutical study within 30 days prior to screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry.
• Patients have had greater than three episodes of severe hypoglycemia within 6 months prior to screening.
• Patients are undergoing therapy for a malignancy, other than basal cell or squamous cell skin cancer.
• Patients have cardiac disease that is Class III or IV, according to the New York Heart Association criteria.
• Patients have a known allergy or hypersensitivity to insulin glargine, AC2993, or excipients contained in these agents.
• Patients have characteristics contraindicating metformin or sulfonylurea use, according to product-specific label, in the opinion of the investigator.
• Patients have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine >=1.5 mg/dL for males and >=1.3 mg/dL for females.
• Patients have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamicpyruvic transaminase greater than three times the upper limit of the reference range.
• Patients have known hemoglobinopathy or chronic anemia.
• Patients are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately prior to screening.
• Patients have used any prescription drug to promote weight loss within 3 months prior to screening.
• Patients have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes them from following and completing the protocol, in the opinion of the investigator.
• Patients fail to satisfy the investigator of suitability to participate for any other reason.