Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Long-term, Multi-centre, International, Randomised Double-blind, Placebo-controlled Trial to Determine Liraglutide Effects on Cardiovascular Events
Brief Summary: This trial is conducted in Africa, Asia, Europe, and North and South America. The aim of this trial is to determine the long term effect of liraglutide on cardiovascular events in subjects with type 2 diabetes.


Options:
A: Inclusion Criteria (for the Randomized Controlled Trial)

1. Participants must have lost ≥ 5% of initial weight in the group lifestyle modification program (during the 14-week diet run-in period).
2. Participants must have a BMI ≥ 30 and ≤ 55 kg/m² or have a BMI ≥ 27 kg/m² with a obesity-related co-morbid condition
3. Age ≥ 21 years and ≤ 65
4. Eligible female patients will be:

   * non-pregnant, evidenced by a negative urine dipstick pregnancy test
   * non-lactating
   * surgically sterile or postmenopausal, or they will agree to continue to use an accepted method of birth control during the study
5. Participants must have a primary care provider (PCP) who is responsible for providing routine care and have a reliable telephone service with which to participate in conference calls

Exclusion Criteria:

1. Pregnant or nursing (or plans to become pregnant in the next 18 months)
2. Current major depressive episode, active suicidal ideation, or history of suicide attempts
3. Use in the past 14 days of monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), tricyclics, lithium, triptans, antipsychotics, cabergoline, linezolid, tramadol, dextromethorphan, tryptophan, bupropion, St. John's Wort, or medicines to treat erectile dysfunction
4. Uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg, or diastolic blood pressure ≥ 100 mm Hg)
5. Type 1 diabetes or type 2 diabetes
6. A fasting glucose ≥ 126 mg/dl or HbA1c ≥ 6.5
7. Recent history of cardiovascular disease (e.g., myocardial infarction or stroke within the past 6 months), congestive heart failure, or heart block greater than first degree
8. Clinically significant hepatic or renal disease
9. Thyroid disease not controlled
10. History of malignancy (except for non-melanoma skin cancer)
11. Use of medications known to induce significant weight loss/gain, including chronic use of oral steroids
12. Psychiatric hospitalization within the past 6 months
13. Self-reported alcohol or substance abuse within the past 12 months, including at-risk drinking (current consumption of ≥ 14 alcoholic drinks per week)
14. Loss of ≥ 10 lb of body weight within the past 3 months
15. History of (or plans for) bariatric surgery
B: Inclusion Criteria: - Type 2 diabetes - Age min. 50 years at screening and concomitant cardiovascular, cerebrovascular or peripheral vascular disease or chronic renal failure or chronic heart failure OR age min. 60 years at screening and other specified risk factors of cardiovascular disease - HbA1c: 7.0% or above - Anti-diabetic drug naive or treated with one or more oral anti-diabetic drugs (OADs) or treated with human NPH insulin or long-acting insulin analogue or premixed insulin, alone or in combination with OAD(s) Exclusion Criteria: - Type 1 diabetes - Use of a glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide, liraglutide or other) or pramlintide or any dipeptidyl peptidase 4 (DPP-4) inhibitor within the 3 months prior to screening (trial start) - Use of insulin other than human NPH insulin or long-acting insulin analogue or premixed insulin within 3 months prior to screening. Short-term use of other insulin during this period in connection with intercurrent illness is allowed, at Investigator's discretion
C: Inclusion Criteria:

* body mass index (BMI) e30 kg/m2 in patients with or without comorbidities, or BMI \>27 kg/m2 in patients with treated or untreated hypertension and/or treated or untreated dyslipidemia.
* stable body weight (variation \<5 kg within 3 months prior to screening visit);

Exclusion Criteria:

* History of very low-calorie diet within 6 months prior to screening visit; or history of surgical procedures for body weight loss (eg, stomach stapling, bypass);
* Presence of any clinically significant psychiatric , neurological or endocrine disease
* Presence of treated or untreated type 1 or type 2 diabetes);
* SBP \>165 mmHg and/or DBP \>105 mmHg on 2 consecutive visits from the screening to the inclusion visit;
* History of myocardial infarction or unstable angina pectoris within 6 months prior to screening visit; and history of stroke within 6 months prior to screening visit;
* Administration of anti-obesity drugs or other drugs for body weight reduction within 3 months prior to screening visit;

The investigator will evaluate whether there are other reasons why a patient may not participate.
D: Inclusion Criteria:

* Female and male subjects, 18 to 65 years of age;
* Have BMI ≥30 and ≤45kg/m² for subjects with uncomplicated obesity, and BMI of ≥27 and ≤45kg/m² for subjects with obesity and controlled hypertension and/or dyslipidemia;
* Normotensive (systolic ≤140 mm Hg; diastolic ≤90 mm Hg). Anti-hypertensive medications are allowed with the exception of alpha-adrenergic blockers and clonidine; medical regimen must be stable for at least 6 weeks prior to randomization;
* Medications for treatment of dyslipidemia are allowed as long as medical regimen has been stable for at least 6 weeks prior to randomization;
* Free of opioid medication for 7 days prior to randomization;
* No clinically significant abnormality of serum albumin, blood urea nitrogen, creatinine, bilirubin, sodium, potassium, chloride, calcium or phosphorus;
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 2.5 x upper limit of normal range (ULN);
* No clinically significant abnormality of hematocrit, white blood cell (WBC) count, white cell differential, or platelets;
* Fasting glucose \< 126 mg/dL on no hypoglycemic agents, fasting triglycerides \<400 mg/dL;
* No clinically significant abnormality on urinalysis;
* TSH within normal limits or normal T3, if TSH is below normal limits;
* Negative serum pregnancy test in women of child-bearing potential;
* Negative urine drug screen;
* IDS-SR scores \< 2 on items 5 (sadness), 6 (irritability), 7 (anxiety/tension) and 18 (suicidality), and IDS-SR total score \< 30;
* Women of child bearing potential had to be non-lactating and agree to use effective contraception throughout the study period and 30 days after discontinuation of study drug;
* Able to comply with all required study procedures and schedule;
* Able to speak and read English;
* Willing and able to give written informed consent.

Exclusion Criteria:

* Obesity of known endocrine origin (e.g., untreated hypothyroidism, Cushing's syndrome, established Polycystic Ovary Syndrome);
* Serious medical conditions (including but not limited to ongoing renal or hepatic insufficiency, Class III or IV congestive heart failure; myocardial infarction, history of angina pectoris, claudication, or acute limb ischemia within the previous 6 months; lifetime history of stroke);
* History of malignancy within the previous 5 years with exception of non-melanoma skin cancer or surgically cured cervical cancer;
* A lifetime history of serious psychiatric illness, including lifetime history of bipolar disorder, schizophrenia or other psychosis, bulimia, or anorexia nervosa;
* Current serious psychiatric illness including severe personality disorder, (e.g. borderline or antisocial), current severe major depressive disorder, recent (previous 6 months) suicide attempt, current active suicidal ideation, or recent hospitalization due to psychiatric illness;
* A response to bipolar disorder questions indicating the presence of bipolar disorder;
* In need of medications for the treatment of a psychiatric disorder (with the exception of short-term insomnia) within the previous 6 months prior to randomization;
* History of drug or alcohol abuse or dependence (with the exception of nicotine dependence) within 1 year prior to study initiation;
* Type 1 or Type 2 diabetes mellitus;
* Screening ECG with a corrected QT interval by the method of Bazett (QTcB) \>450 msec (men) and \> 470 millisecond (msec) (women) or the presence of any clinically significant cardiac abnormalities, including but not limited to patterns consistent with myocardial ischemia, electrolyte abnormalities, or atrial or ventricular dysrhythmia or significant conduction abnormalities;
* Excluded concomitant medications: any psychotropic agents (including antipsychotic, antidepressant, anxiolytic, mood stabilizer, anticonvulsant agents or agents for the treatment of Attention Deficit Disorder) with the exception of low dose benzodiazepine or hypnotic agents for the treatment of insomnia (up to 2 mg lorazepam/day or equivalent dose of a benzodiazepine or hypnotic agent); any anorectic or weight loss agents; any over-the-counter dietary supplements or herbs with psychoactive, appetite or weight effects; alpha-adrenergic blockers; dopamine agonists; clonidine; coumadin; theophylline; cimetidine; oral corticosteroids; cholestyramine, cholestypol, Depo Provera®; smoking cessation agents; use of opioid or opioid-like medications, including analgesics and antitussives;
* History of surgical or device (e.g., gastric banding) intervention for obesity;
* History of seizures of any etiology, or of predisposition to seizures (e.g., history of cerebrovascular accident, head trauma with ≥5 minutes loss of consciousness, concussion symptoms lasting ≥15 minutes, brain surgery, skull fracture, subdural hematoma, or febrile seizures);
* History of treatment with bupropion or naltrexone within the preceding 12 months;
* History of hypersensitivity or intolerance to bupropion or naltrexone;
* Initiation or discontinuation of tobacco products including inhaled tobacco (such as cigarettes, cigars, pipes, etc), chewing tobacco or snuff in the 3 months prior to randomization or planned during study participation. Use of nicotine replacement products (nicotine gum, patch) during study participation was not allowed;
* Use of drugs, herbs, or dietary supplements believed to significantly affect body weight or participation in a weight loss management program within one month prior to randomization;
* Loss or gain of more than 4.0 kilograms within 3 months prior to randomization;
* Pregnant or breast-feeding women or planning to become pregnant during the study period or within 30 days of discontinuing study drug;
* Planned surgical procedure that can impact the conduct of the study;
* Use of investigational drug, device or procedure within the previous 30 days;
* Participation in any previous clinical trial sponsored by Orexigen Therapeutics;
* Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in the study;
* Investigators, study personnel, sponsor representatives and their immediate families.

Answer: B