Effect of DPP4 Inhibition on Growth Hormone Secretion

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.

Conditions

• Obesity

Interventions

DRUG

Sitagliptin

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.

DRUG

Pegvisomant

During Aim 2, given 72 hours prior to one of two study days (Group B subjects only)

DRUG

Placebo

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)

DRUG

L-NMMA

During Aim 2, given during one of two study days (Group A subjects only)

DRUG

Exendin 9-39

During Aim 2, given during one of two study days (Group C subjects only)

Sponsors & Collaborators

• National Institutes of Health (NIH)

  collaborator NIH

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• Vanderbilt University

  lead OTHER

Principal Investigators

• Jessica K Devin, MD, MSCI · Vanderbilt University Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-01-31

Primary Completion

2017-05-31

Completion

2017-05-31

Countries

• United States

Study Locations