The purpose of this study is to compare the effectiveness of two different kinds of diabetes medications, insulin detemir (Levemir) and exenatide (Byetta), in improving blood sugar levels with little or no weight gain in patients with type 2 diabetes who are not well controlled on two or more oral (by mouth) diabetes medications. Both medications are given by injection with a very small needle just below the surface of your skin (called subcutaneous injection). The medication that you inject will be in addition to your oral medications.

Finding a safe and effective method of improving blood glucose (BG) control without weight gain is one of the major goals of diabetes research. Previous research studies have shown that Levemir and Byetta are safe and effective medications in the treatment of type 2 diabetes. Both drugs have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of type 2 diabetes. The use of Levemir and Byetta in combination in this study, is investigational, meaning it is not approved by the FDA for this use. However, the FDA has allowed the use of Levemir and Byetta in combination in this study of safety and effectiveness in improving blood sugar levels with little or no weight gain in people with type 2 diabetes.

Levemir is a long acting insulin that is usually taken once a day at bedtime and can last for up to 24 hours. Unlike most insulins that lower blood glucose levels, but cause weight gain, clinical research trials suggest that Levemir may lower blood glucose levels without causing weight gain and may even result in weight loss.

Byetta is not insulin, but improves blood glucose control by mimicking the action of hormones in the gastrointestinal tract called incretins. The incretin hormones trigger the release of insulin from the pancreas and allow insulin to work more effectively in the body. Byetta also delays the movement of food from the stomach into the small intestine. As a result, people taking Byetta may feel "full" faster and longer, so they eat less. The most common side effect with Byetta is mild to moderate nausea, which improves with time in most people. Clinical research trials that have studied the effects of Byetta have shown that, in addition to lowering blood glucose levels, the use of Byetta resulted in weight loss.

There have been no previous studies that have compared Levemir to Byetta in patients who have failed to achieve blood glucose goals with two or three oral diabetes medications.

Inclusion Criteria:

1. A diagnosis of Type 2 DM for over six months
2. A history of inadequate glycemic control (A1c > 7.5% but < 10%) despite treatment with 2 or more oral hypoglycemic agents
3. 18 years of age or older
4. Stable medical status (e.g., no myocardial infarction, stroke, major surgery, or major mental illness during the previous 6 months)
5. Naïve to insulin (no insulin for more than 14 days during the previous 6 months and none within 60 days of beginning the study)
6. On at least ½ maximum or the greatest tolerable dose of their oral agents according to the label for at least 3 months
7. BMI < 40 kg/m2
8. Willing to perform at least four finger stick blood glucose measurements each day

Exclusion Criteria:

1. A diagnosis of Type 2 DM for less than six months
2. An A1c of < 7.5% or > 10%
3. Pregnancy as determined by a serum ß HCG.
4. An unstable medical status
5. Taking glucocorticoids, amphetamines, anabolic, or weight-reducing agents during the course of the study
6. Inability to read and write English
7. Someone who is not likely to return for the follow-up because they or their sponsor is likely to have a permanent change of station or termination of service before completion of the protocol
8. Unwilling to perform four finger stick blood glucose measurements each day
9. Previous history of use of exenatide