Glucose Homeostasis
Conditions
Keywords
Healthy volunteers, GLP-1, Januvia, Sitagliptin
Brief summary
This research is being done to evaluate the effect of glucagon-like peptide-1 (GLP-1, a naturally occurring hormone) on insulin release and to examine whether there is extra insulin release when GLP-1 is not allowed to be rapidly inactivated.
Detailed description
The purpose of the present proposal is to 1) examine the role of dipeptidyl peptidase (DPP-4) inhibition on insulin release during a hyperglycemic clamp while GLP-1 is being infused and, 2) further elucidate the role of the metabolite of GLP-1, that is GLP-1 9-36 amide (GLP-1m). During stable and very reproducible elevated plasma glucose levels the effect of increased active incretin levels with DPP-4 inhibitors should result in increased plasma insulin levels. Therefore the aim of this protocol is to document whether plasma insulin levels are increased following GLP-1 infusion in the presence or absence of DPP-4 inhibitors. Additionally, the investigators have shown that some improvement in glucose homeostasis during GLP-1 administration is due in part to the metabolite of GLP-1, i.e. GLP-1 (9-36) amide (GLP-1m). Therefore, the investigators will also test the role of the latter by infusing GLP-1m when the volunteers are being treated with DPP-4 inhibitors.
Interventions
DRUGPlacebo
1 tablet 100 mg once a day
DRUGJanuvia
1 tablet 100 mg once a day
Sponsors
Merck Sharp & Dohme LLC
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Hct level of at least 34% for women and 36% for men * Women of non-bearing potential and women of childbearing potential using adequate contraception * Serum creatine level of less than 1.7 mg/dl * Four groups: * Age 21-45 (BMI between 18.50-24.99) & (BMI between 30-35) * Age greater than 65 years (BMI between 18.50-24.99) & (BMI between 30-35)
Exclusion criteria
* Pregnant and/or lactating females * Women of childbearing potential not willing to use adequate contraception * Hct below inclusion criteria * Serum creatine level greater than 1.8 mg/dl * Age less than 21 and age between 46-64 * Diabetes mellitus * BMI less than 18 and BMI greater than 35
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Insulin Release Rate and Hepatic Glucose Release | One year |
Secondary
| Measure | Time frame |
|---|---|
| Peripheral Glucose Utilization and Peripheral Glucagon Release | one year |
Countries
United States
Participant flow
Recruitment details
Although 12 participants were enrolled in this study, their assignment to a specific Arm/Group is unknown, as the PI has left the institution and no further data (if any) is available.
Participants by arm
| Arm | Count |
|---|---|
| All Particpants Januvia: 1 tablet 100 mg once a day
OR
Placebo: 1 tablet 100 mg once a day | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study was terminated,PI left institution | 12 |
Baseline characteristics
| Characteristic | All Particpants |
|---|---|
| Age, Customized >=21 and <=75 | 12 participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Insulin Release Rate and Hepatic Glucose Release
Time frame: One year
Population: Data was not collected for this outcome measure. The study was terminated. The P.I. left the institution.
Secondary
Peripheral Glucose Utilization and Peripheral Glucagon Release
Time frame: one year
Population: Data was not collected for this outcome measure. The study was terminated. The P.I. left the institution.