Liraglutide for HIV-associated Neurocognitive Disorder

Effects of Liraglutide on Cognition, Chronic Inflammation and Glycemic Control in Overweight and Obese, HIV-infected Subjects With Type 2 Diabetes.

This study will test the effect of liraglutide on cognitive function in HIV-infected overweight or obese subjects with type 2 diabetes.

HIV, insulin resistance and type 2 diabetes mellitus (DM) are independently associated with cognitive impairment. Considering the synergistic effects of HIV and DM on cognition, these subjects are at increased risk of cognitive impairment. glucagon-like peptide 1 (GLP-1) receptors have wide tissue distribution including the central nervous system. The study hypothesis is that GLP-1 could potentially ameliorate the impairments in cognition in this population. This study will assess the impact of liraglutide on neurocognitive performance and peripheral inflammatory markers. It will also evaluate the effects of liraglutide on glycemic control and metabolic risk factors in HIV infected subjects with type 2 diabetes.

Inclusion Criteria:

• HIV controlled on therapy for at least 12 weeks
• Viral load < 200 copies
• BMI >27 to 45
• Diagnosis of DM type 2 with A1-C >7 to 15
• Participants must be willing to comply with all study related procedures

Exclusion Criteria:

• Personal or family history of pancreatitis
• Medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia Syndrome Type 2 (MEN 2)
• Gastroparesis
• Allergy to liraglutide or any of the active ingredients in liraglutide or other GLP-1 analogue
• Weight loss drugs other than metformin
• Type 1 diabetes mellitus or diabetic ketoacidosis
• Known major cognitive deficit dementia, history of head trauma with loss of consciousness >30 min, history of stroke, current central nervous system (CNS) disorder such as seizures or opportunistic CNS infection
• Renal insufficiency defined as creatinine clearance < 60 mL/min
• Active opportunistic infections
• Pregnancy or breastfeeding
• Unstable cardiovascular disease with hospitalization within 1 year for acute coronary syndrome
• Decompensated heart failure
• Substance abuse
• Active alcohol or opioid substitution therapy
• Serious or unstable medical or psychological conditions that would compromise the subject's safety for successful participation