Effect of DPP4 Inhibition on Growth Hormone Secretion
Condition: Obesity
MeSH terms: Obesity
Study type: Interventional
Phase: Phase 4

Summary: 
      This study tests the following hypotheses:

      Aim 1: Test the hypothesis that acute dipeptidyl peptidase 4 (DPP4) inhibition with the
      currently available anti-diabetic drug, sitagliptin, will increase stimulated growth hormone
      (GH) secretion in healthy lean adults by decreasing the degradation of growth hormone
      releasing hormone (GHRH).

      Aim 2: Test the hypothesis that decreased degradation of GHRH during acute DPP4 inhibition
      will result in an increase in endothelium-dependent vasodilation mediated by GH and
      independent from GLP1 (glucagon like peptide-1) in healthy lean adults.

      This study promises to provide novel data regarding how this increasingly used class of
      anti-diabetic drugs affects the pituitary GH axis and could affect blood vessel relaxation.
      Growth hormone levels are low in the setting of obesity and pre-diabetes. A further study may
      evaluate the effect of chronic DPP4 inhibitor therapy in a population of patients with
      obesity and pre-diabetes.
    

Detailed description: 
      Growth hormone secretion is low in patients with obesity, insulin resistance, and
      hyperlipidemia. GH therapy in these populations and others has been limited by side effects
      which include hyperglycemia. Another strategy to increase GH secretion is to enhance
      pulsatile GH secretion by growth hormone releasing hormone. Growth hormone releasing hormone
      (GHRH) has a half life of 5 minutes due to its rapid inactivation by DPP4. An alternative
      strategy to increase endogenous GH secretion is by inhibiting degradation of GHRH by DPP4.
      DPP4 inhibitors are currently approved therapies for the treatment of hyperglycemia in
      patients with type 2 diabetes mellitus. They additionally cause blood vessel relaxation. We
      therefore propose to test the hypothesis that DPP4 inhibition simultaneously enhances GH
      secretion while improving blood glucoses and vascular function in patient populations with
      low GH and increased cardiovascular risk. These preliminary aims serve primarily as a novel
      "proof of concept" study to define the effect of acute pharmacologic DPPIV inhibition on
      stimulated GH secretion.
    

Intervention name(s): Sitagliptin; Pegvisomant; Placebo; L-NMMA; Exendin 9-39
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): During Aim 1, given on one of two study days (other study day subjects receive placebo.) During Aim 2, given during both of two study days.; During Aim 2, given 72 hours prior to one of two study days (Group B subjects only); During Aim 1, given on one of two study days (other study day subjects receive sitagliptin.) During Aim 2, given on one of two study days (other study day subjects receive either L-NMMA, pegvisomant, or Exendin 9-39 pending their group assignment); During Aim 2, given during one of two study days (Group A subjects only); During Aim 2, given during one of two study days (Group C subjects only)
Other intervention name(s): Januvia; Somavert; sugar pill; L-N-Monomethyl-arginine
Intervention MeSH terms: Sitagliptin Phosphate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: obesity; growth hormone