Clinical trial NCT02683187: DPP4 Inhibition & Beta Cell Function
Official title: Role of Alpha-cell GLP-1 in the Beta-cell Response to DPP-4 Inhibition
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: insulin secretion
GLP-1
alpha cell
paracrine effect
Glucagon-Like Peptide 1
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-02-17
Enrollment: 40
Sex: ALL
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Arginine-stimulated Insulin Secretion With and Without GLP-1 Blockade
timeFrame: 30 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Leslie Willis
state: North Carolina
Study officials:
References:
citation: Gray SM, Hoselton AL, Krishna R, Slentz CA, D'Alessio DA. GLP-1 Receptor Blockade Reduces Stimulated Insulin Secretion in Fasted Subjects With Low Circulating GLP-1. J Clin Endocrinol Metab. 2022 Aug 18;107(9):2500-2510. doi: 10.1210/clinem/dgac396.