A Pilot Study of the Effects on Sleep Disordered Breathing (SDB) When Using the Drug Liraglutide for 4 Weeks

This is a pilot study aimed at measuring the change in obstructive apnea/hypopnea index in
non-diabetic patients being treated for the first time with the glucagon-like peptide-1
(GLP-1) agonist, Liraglutide. Sleep disordered breathing (SDB) consists of nocturnal alveolar
hypoventilation and / or obstructive sleep apnea which result from abnormalities in upper
airway tone and ventilation during sleep. The development of a new pharmacological treatment
for sleep disordered breathing (SDB) could bring a breakthrough discovery that will impact a
rapidly growing population of children and adults with this disorder. The investigators
hypothesize that GLP-1 plays a central role in the improvement of SDB and that the
administration of GLP-1 receptor agonist to patients with OSA will correct or improve SDB.

- Hypothesis 1: Administration of Liraglutide to patients with severe OSA defined as apnea
hypopnea index ≥ 8 /hr. will result in a mean reduction in the index by a minimum of 50%
after 4 weeks.

- Hypothesis 2: Administration of Liraglutide will result in significant increase in
Orexin level, decrease in leptin, decrease in Epworth Sleepiness Scale (ESS) score and
increase in carbon dioxide (CO2) chemosensitivity.

This is an open label, non-randomized, controlled pilot study. Subjects are heavy to obese
non-diabetic adults that are diagnosed with sleep apnea. 20 subjects will be treated with
liraglutide for 4 weeks and compared to 10 untreated controls.

Study time points are baseline and 4 weeks post treatment. Study procedures include pre and
post treatment: fasting blood for glucose, hemoglobin A1C (HbA1C), Orexin and leptin; ESS
questionnaire; pulmonary function test and hypercapnic challenge. The procedures also include
a post treatment overnight research sleep study to measure change in apnea index from
diagnostic sleep study done previous to study enrollment or if needed, the baseline research
sleep study.

Inclusion Criteria:

- Age 18-60 years

- Diagnosis of severe obstructive sleep apnea (OSA) AHI ≥ 8 /hour of sleep

- Ability and willingness to comply with all protocol procedures e.g. correct handling
of trial product, compliance to visit schedule

- BMI of ≥ 27

- For Cohort 1: If female of childbearing capacity, willing to use acceptable birth
control during use of study drug

Exclusion Criteria:

- A major medical condition such as renal or hepatic failure

- Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl
peptidase-4 inhibitors or insulin within the last 3 months prior to screening

- Diagnosis of type 1 or type 2 diabetes per judgment of the investigator

- BMI < 27

- History of glycosylated hemoglobin (HbA1c) equal to or above 6.5%

- Significant craniofacial abnormalities that may cause OSA

- Respiratory and neuromuscular diseases that could interfere with the results of the
trial in the opinion of the investigator

- Use of central stimulants, hypnotics, mirtazepine, opioids, trazodone or drugs in the
incretin family within the previous 3 months prior to screening

- Previous surgical treatment for obesity

- Familial or personal history of Multiple Endocrine Neoplasia type 2 or familial
Medullary Thyroid Carcinoma

- Personal or immediate family history of thyroid cancer

- History of chronic pancreatitis or idiopathic acute pancreatitis

- History of Major Depressive Disorder or suicide attempts

- Systolic blood pressure equal to or above 160 mmHg and/or diastolic blood pressure
equal to or above 100 mmHg

- History of alcoholism

- Pregnancy or breastfeeding