Sitagliptin's Effects on Glucose-stimulated Insulin Secretion and Oral Glucose
Trial Snapshot
- Phase
- Phase 4
- Status
- Not yet recruiting
- Enrollment
- 400
- Locations
- 1
- Primary Endpoint
- Sitagliptin-induced enhancement of early insulin secretion
Study Overview
Brief Summary
This is a research study to find out how different people respond to a medication called sitagliptin. Sitagliptin is an FDA approved medication that is used to treat diabetes. We are asking for healthy, non-diabetic volunteers to participate in this 7-week study. If you agree to participate, you will take part in 2 clinic visits that are 4-6 weeks apart. At the clinic visits you will have an oral glucose tolerance test (OGTT) and other blood tests to see how your body processes glucose (sugar). An OGTT is a test in which your drink glucose and then blood samples are taken afterward at specific time points to measure glucose and insulin in your blood. Each clinic visit will last about 5 hours.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •• Age: >18 years old
- •Members of Old Order Amish community in Lancaster, PA
Exclusion Criteria
- •• Pregnancy (reproductive age women will undergo pregnancy tests immediately before receiving the drug)
- •Diabetes: HbA1c > 6.5% or fasting plasma glucose >126 mg/dL
- •Estimated glomerular filtration rates (eGFR) <60 mL/min/1.73 m2
- •Anemia: hematocrit < 35%
- •Thyroid status: TSH<0.4 or TSH>5.5
- •ALT or AST in excess of 2X upper limit of normal
- •Drugs that in the physician's judgment would alter response to sitagliptin
- •Significant health issues that in the physician's judgment could increase the risk for participants.
Arms & Interventions
Sitagliptin
Sitagliptin 100 mg given 2 hours prior to the oral glucose tolerance test
Intervention: Oral Glucose Tolerance Test (Procedure)
Placebo
Placebo given 2 hours prior to the oral glucose tolerance test
Intervention: Oral Glucose Tolerance Test (Procedure)
Outcomes
Primary Outcomes
Sitagliptin-induced enhancement of early insulin secretion
Time Frame: 6 weeks
This represents the incretinomimetic effect of sitagliptin, which contributes importantly to the mechanism whereby DPP4is decrease HbA1c in T2D patients. Because histograms for sitagliptin-induced increase in our index of early insulin secretion (T30:T60) demonstrated a skewed distribution, we will apply a logarithmic transformation of data which yields a normal distribution. Thus, the drug effect is defined as: log(T30:T60 ins)sita - log(T30:T60 ins)control.
Sitagliptin-induced change in glucose tolerance
Time Frame: 6 weeks
Sitagliptin-induced change in glucose tolerance. This is a consequence of enhanced insulin secretion, which reflects most closely the desired effect of the drug to decrease plasma glucose and decrease HbA1c. Because histograms for sitagliptin-induced increase in our index of glucose tolerance (T30:T60) demonstrated a skewed distribution, we will apply a logarithmic transformation of data which yields a normal distribution. Thus, the drug effect is defined as: log(T30:T60 gluc)sita - log(T30:T60 gluc)control.
Secondary Outcomes
- Area under the curve for C-peptide levels(6 weeks)
- Area under the curve for insulin concentration(6 weeks)
- Area under the curve for glucose concentration(6 weeks)
- Area under the curve for intact GIP(6 weeks)
- Area under the curve for intact GLP1(6 weeks)
Investigators
Amber Beitelshees
Professor
University of Maryland, Baltimore