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NCT Number: NCT02683187

DPP4 Inhibition & Beta Cell Function

This study is being done to determine the role of a hormone, glucagon-like peptide 1 (GLP-1), on insulin secretion and to study how GLP-1 works in in diabetic individuals as compared to non-diabetic individuals, under fasting conditions.

GLP-1 is a naturally occurring hormone made in the intestines. It is released into the circulating blood after eating and helps to control the blood glucose levels by increasing insulin secretion by cells in the pancreas. However, the exact method by which GLP-1 causes insulin secretion and how GLP-1 activity is changed in diabetic persons remain unclear. This research is being done to address these questions and better understand the function of GLP-1.

In this research, the investigators will use a synthetic form of Exendin-9 to determine the effects of GLP-1 on insulin secretion in diabetic and non-diabetic persons. Exendin-9 acts as a blocker of GLP-1 action, allowing us to study the specific effects of the GLP-1 hormone. Exendin-9 is an investigational compound, which means it is still being tested in research studies and is not approved by the U.S. Food and Drug Administration (FDA).

In this study, the investigators will also use the drug Sitagliptin, which is an FDA-approved drug for the treatment of type 2 diabetes mellitus. In this study, use of Sitagliptin is considered investigational since it is not being used for treatment of diabetes but is instead being used to understand how GLP-1 works and to better understand how medications like Sitagliptin work in patients with type 2 diabetes mellitus.

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Key information

Conditions

Healthy

Age range

35 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Leslie Willis

Durham, North Carolina, 27707, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diabetic cohort: adults age 35-70 years with Type 2 diabetes managed by an oral medication or diet and exercise
  • Non-diabetic cohort: healthy adults age 35-70 years
  • Male or female
  • Ability to speak and understand English
  • Diabetic cohort: HbA1c ≤ 8.0%
  • Non-diabetic cohort: HbA1c ≤ 6.2%

Exclusion criteria

  • Rheumatoid arthritis
  • Inflammatory bowel disease
  • Unstable angina or uncompensated heart failure
  • Pulmonary disorders, including COPD and asthma
  • Malabsorptive GI disease, such as celiac disease, or gastric bypass
  • Significant hepatic disease
  • Renal insufficiency (eGFR < 60 mL/kg/min)
  • Anemia (hematocrit < 34%) as measured at screening visit
  • Uncontrolled hypertension
  • Pregnant females
  • Consumption of daily medications that alter glucose metabolism of GI function (glucocorticoids, psychotropics, narcotics, metoclopramide)
  • Consumption or injection of insulin
  • Apparent sensitivity to any of the study peptides as determined by the skin test

Treatment and study plan

Active Comparator: Sitagliptin

Drug

Subjects will receive sitagliptin prior to the start of the experiment involving 1/2 of the subjects receiving Exendin-9 (a GLP-1 receptor blocker) first over 60 minutes ; followed by a bolus arginine (5g) infusion after 30 minutes into the Ex-9 infusion, with blood draws over the next 30 minutes. Followed by a 60 minute washout and the procedure is repeated , this time with saline instead of Ex-9 (these procedures are reversed - saline first then Ex-9 - half of the time).

Placebo Comparator - No Sitagliptin

Drug

Subjects will receive Placebo (instead of sitagliptin) prior to the start of the experiment involving 1/2 of the subjects receiving Exendin-9 (a GLP-1 receptor blocker) first over 60 minutes ; followed by a bolus arginine (5g) infusion after 30 minutes into the Ex-9 infusion, with blood draws over the next 30 minutes. Followed by a 60 minute washout and the procedure is repeated , this time with saline instead of Ex-9 (these procedures are reversed - saline first then Ex-9 - half of the time).

Primary outcomes

  1. Arginine-stimulated Insulin Secretion With and Without GLP-1 Blockade

    Time frame: 30 minutes

    The investigators will use the mean increment of insulin secretion rate above baseline in the 30 minutes after Arginine stimulation to integrate insulin secretion, the primary outcome measure, and 2-way ANOVA with and without Sitagliptin and Ex-9/saline at the two factors.

Sponsors and collaborators

Lead sponsor

David D'Alessio, M.D.

Other

Collaborators

  • Merck Sharp & Dohme LLC

Registry information

Official study title

Role of Alpha-cell GLP-1 in the Beta-cell Response to DPP-4 Inhibition

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Feb 17, 2016
Registry last updated
May 3, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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