This study will examine the safety, tolerability, and body weight effect of subcutaneous pramlintide alone and in various combinations with the oral antiobesity agents sibutramine or phentermine in overweight and obese subjects.

Inclusion Criteria:

• Is obese with a Body Mass Index (BMI) >=30 kg/m^2 to <=50 kg/m^2 or overweight with a BMI >=27 kg/m^2 in the presence of other risk factors (e.g., hyperlipidemia, sleep apnea, or treatment for these conditions)
• Has been obese or overweight for at least one year prior to study start
• Either is not treated with or has been on a stable treatment regimen with any of the following medications for a minimum of 2 months prior to study start: *hormone replacement therapy; *oral contraceptives; *lipid-lowering agents; *thyroid replacement therapy; *metformin

Exclusion Criteria:

• Is currently enrolled in or is planning to enroll in a formal weight-loss program
• Is unwilling or unable to participate in a lifestyle intervention program as part of the study
• Has been treated (within the 2 months prior to study start), is currently treated, or is expected to require or undergo treatment with any of the following excluded medications: *prescription or over the counter antiobesity agents (within the 6 months prior to study start); *psychotropic/neurological agents (i.e., antipsychotic, antiepileptic, antidepressant, or antianxiety agents, or mood stabilizers); *steroids that are known to result in high systemic absorption; *calcitonin; *ketoconazole; *antidiabetic medications
• Has had liposuction, abdominoplasty, or a similar procedure within 1 year before study start or is planning to have such a procedure during the study
• Has received any investigational drug within 1 month (or 5 half-lives of investigational drug, whichever is greater) before study start
• Has previously used pramlintide either by prescription or as part of a clinical study
• Has used sibutramine or phentermine (either by prescription or as part of a clinical study) within 2 years before study start
• Has donated blood within 2 months before study start, or is planning to donate blood during the study