Effect of Liraglutide (Victoza) on Inflammation in Human Adipose Tissue and Blood
Condition: Diabetes Mellitus, Type 2; Diabetes Mellitus, Type II; Diabetes Mellitus, Adult-Onset; Inflammation
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Inflammation
Study type: Interventional
Phase: Phase 1

Summary: 
      The objective of this study is to test the hypothesis that liraglutide (commonly known as
      Victoza) can promote an anti-inflammatory macrophage phenotype in human adipose tissue and
      blood, thereby reducing localized and systemic inflammation which are risk factors for
      cardiovascular disease and may contribute to hyperglycemia. This will be done after 4 weeks
      of treatment during which weight will remain stable, and again after 12 weeks, during which
      liraglutide-related weight loss occurs.
    

Detailed description: 
      It has now been established that the high risk of cardiovascular disease that is associated
      with obesity and type 2 diabetes is related to the systemic inflammation that underlies these
      conditions. Previous studies have shown that there are numerous types of immune cells in
      human adipose tissue, some of these are the macrophages. These cells can exist in two states:
      M2, which can inhibit classical inflammatory response, and M1 which secrete proinflammatory
      cytokines. The investigators have data to suggest that the role of inflammatory cells in
      adipose tissue is a strong contributor to systemic inflammation. A recent study showed that a
      GLP-1 analog (liraglutide, also known as Victoza) may help decrease inflammation via
      promoting M2 differentiation of macrophages. The purpose of this study is to quantify
      macrophage phenotype (M1 vs M2) in subcutaneous adipose tissue in moderately-obese diet
      controlled diabetics at baseline, after four weeks of weight-maintenance using liraglutide,
      and after 12 weeks of liraglutide treatment as compared to placebo.

      Aim 1: Quantify M1 and M2 (surface and intracellular markers) polarization via flow cytometry
      in subcutaneous abdominal adipose tissue and peripheral blood mononuclear cells at baseline
      and after 4 weeks administration of liraglutide versus placebo to weight-stable, obese, type
      2 diabetic patients. Weight loss will be prevented in order to ascertain the effect of
      liraglutide alone.

      Aim 2: Quantify M1 and M2 (surface and intracellular markers) polarization via flow cytometry
      in subcutaneous adipose tissue and peripheral blood mononuclear cells after 12 weeks of
      liraglutide treatment, during which dietary restrictions are lifted and spontaneous weight
      loss, as would occur in the clinical setting, is allowed. To eliminate confounding by weight
      loss, a placebo-treated group will undergo matched dietary weight loss for comparison to the
      liraglutide group to ascertain whether changes in macrophage polarization at 12 weeks are
      greater in the liraglutide group.

      Aim 3: Quantify macrophage-mediated localized and systemic inflammation by measuring
      M1/M2-related inflammatory cytokines in adipose tissue and peripheral blood after 4 and 12
      weeks administration of liraglutide versus placebo to obese, type 2 diabetic patients.
    

Intervention name(s): Victoza (liraglutide) with dietician monitoring; Placebo with dietician monitoring
Intervention type(s): Drug; Other
Intervention description(s): Victoza (liraglutide), an FDA-approved medication, is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Subjects with this intervention will be followed by the MD and dietician throughout the study to monitor progress through 4 week period of weight maintenance and 8 week period of weight loss.; Subjects will not receive the study drug, but will be followed by the MD and dietician throughout the study to monitor progress through 4 week period of weight maintenance and 8 week period of weight loss.
Other intervention name(s): liraglutide
Intervention MeSH terms: Liraglutide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: diabetes; macrophage; inflammation; adipose tissue; weight loss; liraglutide