DPP4 Inhibition & Beta Cell Function

• Status: Completed
• Trial end date: 2018-03-16
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: David D'Alessio, M.D.
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Sitagliptin Phosphate

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