Please select the eligibility criteria that correspond to the clinical trial below.
Title: Time Course of the Blood Pressure Lowering Effect of Liraglutide Therapy in Type 2 Diabetes
Brief Summary: Background: Preclinical blood pressure (BP) data from studies of hypoglycemic effects of liraglutide treatment (the LEAD program), revealed a significant antihypertensive potential. The time course and the mechanism behind this effect are unknown.

Objectives: To evaluate the time course of the antihypertensive effect of liraglutide treatment in patients with type 2 diabetes

Design: Open-label study with intervention and subsequent washout period

Patient Population: 35 hypertensive (SBP ≥130 mm Hg and DBP ≥80 mmHg) patients with type 2 diabetes.

Intervention: All patients will be treated with liraglutide 0.6 mg once daily for 7 days and will then be titrated to 1.2 mg once daily for 14 days and then titrated to 1.8 mg once daily for 4 weeks. This is followed by a washout period of 3 weeks without liraglutide treatment.

Endpoints: 24-hour blood pressure, natriuresis, extra cellular volume (ECV


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:

* Informed Consent
* BMI ≥ 27 (no lower BMI limit for Type 2 diabetics)
* 70 years of age or less
* Have 2 or more of the following obesity-related co-morbid conditions:

  * Systolic blood pressure 140-160 mmHg (130-160 if diabetic);
  * Diastolic blood pressure 90-100 mmHg (85-100 if diabetic);
  * Requirement for 2 or more medications to achieve control (\<140/90 mmHg)
* Triglyceride level between 200-400 mg/dL or requirement for 2 or more medications to achieve control (\<200 mg/dL)
* At lease one of the following metabolic criteria:

  * Fasting blood glucose level \> 100 mg/dL
  * Glucose level \> 140 mg/dL
  * Diagnosis of type 2 diabetes
* Waist circumference ≥ 102 cm for men or ≥88 cm for women

Exclusion Criteria:

* Stroke/MI/unstable cardiovascular disease within 6 months
* Clinically significant renal, hepatic or psychiatric disease
* Unstable thyroid disease or replacement therapy
* Nephrolithiasis
* Obesity of known genetic or endocrine origin
* Participation in a formal weight loss program or lifestyle intervention
* Glaucoma or intraocular pressure
* Pregnancy or breastfeeding
* Drug or Alcohol abuse
* Smoking cessation within previous 3 months or plans to quit smoking during study
* Eating disorders
* Cholelithiasis within past 6 months
* Excluded medications
* Type 1 diabetes or use of any antidiabetic medication other than metformin
* Previous bariatric surgery
* Bipolar disorder or psychosis
* Steroid hormone therapy
* Systolic blood pressure \> 160 mmHg, diastolic blood pressure \> 100 mmHg
* Creatinine clearance \< 60 mL/minute
C: Inclusion Criteria:

1. Must give written informed consent before participation. Patient information and consent form must be approved by the Danish Medicines Agency and the Regional Scientific Ethical Committee
2. Male or female patients \> 18 years with type 2 diabetes (WHO criteria).
3. Patients must be on treatment with metformin. Any form of treatment with SU compounds will be discontinued and washed out for two weeks prior to the start of study drug.
4. eGFR ≥ 60 ml/min/1.73 m2 (estimated by MDRD formula)
5. Fertile female patients must use chemical, hormonal and mechanical contraceptives or be in menopause (i.e. must not have had regular menstrual bleeding for at least one year) or have undergone bilateral oophorectomy or have been surgically sterilized or hysterectomised at least six months prior to screening
6. Patients must be on antihypertensive treatment or having elevated blood pressure (SBP ≥130 mm Hg and DBP ≥80 mmHg), lower than 170/105 mm Hg at baseline and the patients must be stable antihypertensive medication for at least 4 weeks prior to baseline
7. Patients must be on stable hypoglycemic medication for at least two weeks before the first visit.
8. Must be able to communicate with the investigator

Exclusion Criteria:

1. Ongoing insulin therapy
2. BP \> 170/105 mm Hg at baseline
3. Type 1 diabetes mellitus
4. Chronic pancreatitis / previous acute pancreatitis
5. Known or suspected hypersensitivity to trial product(s) or related products.
6. Treatment with oral glucocorticoids, calcineurin inhibitors, or dipeptidyl peptidase 4 (DPP4) inhibitors which in the Investigator's opinion could interfere with glucose or lipid metabolism 90 days prior to screening
7. Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder, except for conditions associated with type 2 diabetes history, which in the investigators opinion could interfere with the results of the trial
8. Inflammatory bowel disease
9. Cardiac disease defined as: Decompensated heart failure (NYHA class III-IV) and/or diagnosis of unstable angina pectoris and/or myocardial infarction within the last 6 months
10. Previous bowel resection
11. Body mass index \<18.5 kg/m2
12. Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods
13. Clinical signs of diabetic gastroparesis
14. Impaired liver function (transaminases \> two times upper reference levels)
D: Inclusion Criteria:

* Overweight/obese men and women with type 2 diabetes mellitus that is managed with oral anti-hyperglycemic agent(s).
* Body mass index (BMI) 27 to 45 kg/m2, inclusive.
* Ability to complete a 1 year study

Exclusion Criteria:

* Pregnancy
* Use of insulin in any form, exenatide (Byetta) or pramlintide (Symlin) within 3 months prior to screening
* History of symptomatic heart valve disease
* Serious or unstable current or past medical conditions

Answer: C