Effectiveness of Sitagliptin for HIV Insulin Resistance and Inflammation
Condition: Inflammation; Macrophage Infiltration; Cardiovascular Disease
MeSH terms: Cardiovascular Diseases; Insulin Resistance; Inflammation
Study type: Interventional
Phase: Phase 3

Summary: 
      People living with human immunodeficiency virus infection (HIV) have 2-4fold greater risk for
      developing diabetes and heart disease than the general population. They need safe and
      effective treatments that reduce the risk for developing diabetes and heart disease, and
      improve their quality of life. This project will explore whether a new anti-diabetes
      medication (Januvia) with a novel mechanism of action reduces inflammation, and improves
      blood vessel function in HIV infected men and women with several risk factors for developing
      cardiovascular disease.
    

Detailed description: 
      People living with human immunodeficiency virus (HIV+) infection have a 2-fold greater
      prevalence and incidence of T2DM and cardiovascular disease (CVD) than the general
      population. The investigators lack safe and effective treatments for these HIV related
      cardiometabolic complications despite the fact that HIV infected adults represent an ideal
      clinical population in which to study interactions among chronic low-grade pro-inflammatory
      processes that are linked to the development of adipose accumulation, insulin resistance,
      ß-cell secretory failure, vascular endothelial dysfunction, atherosclerosis and CVD.
      Dipeptidyl peptidase-IV (DPP4)-inhibitors represent a new drug class that safely and
      effectively regulate glycemia in T2DM, but have not been adequately tested in HIV. Of note,
      pre-clinical studies suggest that DPP4-inhibitors have several pleiotropic actions that may
      specifically benefit people living with HIV infection. For example, DPP4 inhibition reduced
      adipose macrophage infiltration & inflammation and increased the number of bone-derived
      endothelial progenitor cells in the circulation. Our preliminary findings indicate that DPP4
      inhibition is virologically and immunologically safe in non-diabetic HIV+ adults taking
      combination antiretroviral therapy (in preparation), but the potential pleiotropic benefits
      have not been examined in HIV. The investigators propose a randomized, double blind, placebo
      controlled physiological study to test 2 potential pleiotropic benefits of DPP4 inhibition
      (100 mg sitagliptin/d, 8 wk): reduce circulating and adipose-specific markers of
      inflammation; and increase endothelial progenitor cell numbers used for vascular repair in 36
      HIV+ adults with insulin resistance, central adiposity and CVD risk factors. The
      investigators hypothesize that sitagliptin will reduce circulating cytokine levels, reduce
      adipose tissue macrophage number and inflammation, and increase the number of circulating
      endothelial progenitor cells in HIV infected men and women. These physiological studies will
      advance our understanding about the efficacy of DPP4 inhibition in this high-risk group, and
      may help prevent the inexorable transition from insulin resistance to T2DM and CVD in HIV
      infected men and women.
    

Intervention name(s): Sitagliptin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Oral, 100 mg/day for 2 months; oral, matching placebo daily for 2 months
Other intervention name(s): Januvia
Intervention MeSH terms: Sitagliptin Phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: cardiometabolic complications