The Effects of Liraglutide on Sudomotor Function and Inflammation in Type 2 Diabetes

This is an interventional prevention trial for Autonomic Nervous System Diseases Read More

Inclusion Criteria:

1. established type 2 diabetes (diabetes duration of >6 months and <10 years).
2. Age 18-80 years
3. HbA1c at screening ≤ 10%
4. Subjects on stable (≥3 months prior to Screening) Standard of Care background diabetic therapy. Diabetic treatment regimens include diet and exercise alone or in association with oral anti-diabetic drugs (monotherapy or combinations) and/or long-acting insulin.

Exclusion Criteria:

1. Presence of type 1 diabetes mellitus (defined as C-peptide <1 ng /ml, <35y and prone to ketoacidosis)
2. Treatment with rapid-acting or short-acting insulin within the last 3 months
3. Proliferative retinopathy or maculopathy requiring acute treatment
4. Impaired renal function , defined as serum creatinine ≥ 125 µmol/L (≥1.4 mg/dL) for males and ≥ 110 µmol/L (≥1.24 mg/dL) for females
5. Impaired liver function, defined as aspartate transaminase (AST) or alanine transaminase (ALT), ≥ 2.5 times the upper limit of normal
6. Presence of clinically significant peripheral or autonomic neuropathy that is clearly of non-diabetic origin
7. Uncontrolled treated/untreated hypertension (systolic blood pressure (BP) ≥180 or diastolic blood pressure (BP) ≥100 at screening)
8. Clinically significant active macrovascular disease including myocardial infarction or cerebrovascular event within the past 6 months. Other exclusions include coronary artery bypass graft or coronary angioplasty in the previous 3 months, unstable angina pectoris (chest pain at rest, worsening chest pain, or admission to the emergency room (ER) or hospital for chest pain) within the previous 3 months, and/or congestive heart failure (NYHA Class III-IV)
9. Subjects known to be Hepatitis B surface antigen or Hepatitis C antibody positive with active hepatitis.
10. Active infection (e.g., human immunodeficiency virus (HIV), hepatitis), or a history of severe infection during the 30 days prior to screening
11. Evidence of immunocompromised status, including but not limited to individuals who have undergone organ transplantation, who are known to be HIV positive, or who are taking immunosuppressive drugs or chronic systemic corticosteroid treatment.
12. Major surgical procedure during the 30 days prior to screening
13. Diagnosis and/or treatment of malignancy (except for basal cell or squamous cell skin cancer, in-situ carcinoma of the cervix, or in-situ prostate cancer) within the past 5 years
14. Known clinically significant gastric emptying abnormality (e.g. severe gastroparesis), or history of gastric bypass (bariatric) surgery
15. Thyroid stimulating hormone (TSH) outside of normal limits at screening, or presence of a thyroid nodule detected on physical examination that has not been fully evaluated
16. Thyroid hormone therapy that has not been stable for ≥6 weeks prior to Screening
17. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN-2)
18. History of acute or chronic pancreatitis
19. Subjects taking medications that are known to affect autonomic function need to be at a stable dose of those medications ≥ 3 months prior to inclusion in the study
20. Other clinically significant, active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, genitourinary or hematological system that, in the opinion of the investigator, would compromise the subject's participation in the study, might confound the results of the study or pose additional risk in administering the study drug
21. Recurrent severe hypoglycemia and/or hypoglycemia unawareness.
22. Concurrent participation in another clinical trial with use of an experimental drug or device within 30 days of study entry.
23. Known or suspected history of alcohol or substance abuse
24. Mental incapacity, unwillingness or language barrier precluding adequate understanding of or cooperation with the study.
25. Women of childbearing potential (WOCBP*) who are pregnant, breast-feeding or intend to become pregnant
26. WOCBP* must have a negative pregnancy test at Screening and must agree to use adequate contraceptive methods** during the study and for one additional menstrual cycle following the end-of-treatment visit
27. Known or suspected hypersensitivity to study product(s) or related products
28. Patients with low vitamin B12 levels will be excluded
29. Current use or use 6 months prior to study participation of dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon like peptide-1 (GLP-1) agonists will be excluded
30. Liraglutide has not been studied in combination with prandial insulin. Patients who use prandial insulin may be excluded