DPP4 Inhibition & Beta Cell Function

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Placebo Comparator - No Sitagliptin

Registration Number: NCT02683187

Lead Sponsor: David D'Alessio, M.D.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Non-Sitagliptin	Placebo Comparator - No Sitagliptin	The infusion procedures performed during study visits 2 and 3 are identical except that the oral medicine Sitagliptin will only be administered at one of the two visits, with order of Sitagliptin administration determined at random by study staff. In this arm, placebo will be administered

Primary Outcome Measures

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

Secondary Outcome Measures