Trial Outcomes & Findings for Pharmacogenomics of GLP1 Receptor Agonists (NCT NCT05762744)

NCT ID: NCT05762744

Last Updated: 2025-07-01

Results Overview

The ratio of the area-under-the-curve (AUC) for 1st phase insulin secretion in the exenatide-stimulated FSIGT divided by the AUC for 1st phase insulin secretion in the saline FSIGT.

• Recruitment status: TERMINATED
• Study phase: PHASE1
• Target enrollment: 63 participants
• Primary outcome timeframe: 0-10 minutes
• Results posted on: 2025-07-01

Participant Flow

Dates: June 2016 - November 2018 Site: Community-based recruitment at Amish Research Clinic, Lancaster Pennsylvania (Univ. of Maryland School of Medicine)

Participants were assigned to specific arms of the study based on the order in which they were randomized to a subcutaneous injection of either exenatide or normal saline solution: Arm 1: Exenatide followed by Normal Saline Arm 2: Normal Saline followed by Exenatide Frequently sampled intravenous glucose tolerance tests (FSIGT) were initiated 15 minutes after the subcutaneous injections of exenatide or normal saline. The second FSIGT was performed 5-28 days after the first FSIGT.

Participant milestones

Measure	Exenatide Followed by Normal Saline Of the 54 participants in our study, 26 individuals were randomized to receive exenatide 15 min before the first frequently sampled intravenous glucose tolerance test (FSIGT) and saline 15 min before the second FSIGT	Normal Saline Followed by Exenatide Of the 54 participants in our study, 26 individuals were randomized to receive normal saline 15 min before the first frequently sampled intravenous glucose tolerance test (FSIGT) and exenatide 15 min before the second FSIGT
1st iv Glucose Tolerance Test STARTED	31	32
1st iv Glucose Tolerance Test COMPLETED	26	26
1st iv Glucose Tolerance Test NOT COMPLETED	5	6
2nd iv Glucose Tolerance Test STARTED	26	26
2nd iv Glucose Tolerance Test COMPLETED	26	26
2nd iv Glucose Tolerance Test NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Exenatide Followed by Normal Saline Of the 54 participants in our study, 26 individuals were randomized to receive exenatide 15 min before the first frequently sampled intravenous glucose tolerance test (FSIGT) and saline 15 min before the second FSIGT	Normal Saline Followed by Exenatide Of the 54 participants in our study, 26 individuals were randomized to receive normal saline 15 min before the first frequently sampled intravenous glucose tolerance test (FSIGT) and exenatide 15 min before the second FSIGT
1st iv Glucose Tolerance Test Withdrawal by Subject	0	1
1st iv Glucose Tolerance Test Some critical blood samples not collecte	5	5

Baseline Characteristics

Pharmacogenomics of GLP1 Receptor Agonists

Baseline characteristics by cohort

Measure	Exenatide First Followed by Normal Saline n=26 Participants Exenatide (5 mcg, sc) was injected 15 minutes before the first frequently sampled iv glucose tolerance test (FSIGT). After a washout period of 5-28 days, participants underwent a second FSIGT with saline (0.20 mL) being injected 15 min before the 2nd FSIGT.	Normal Saline Followed by Exenatide n=26 Participants Saline (0.2 mL) was injected 15 minutes before the first frequently sampled iv glucose tolerance test (FSIGT). After a washout period of 5-28 days, participants underwent a second FSIGT with exenatide (5 mcg) being injected 15 min before the 2nd FSIGT.	Total n=52 Participants Total of all reporting groups
Age, Continuous	50.2 Years n=5 Participants	44.6 Years n=7 Participants	47.3 Years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	13 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	13 Participants n=7 Participants	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants	26 Participants n=7 Participants	52 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	26 Participants n=5 Participants	26 Participants n=7 Participants	52 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	26 participants n=7 Participants	52 participants n=5 Participants
Body Mass Index	28.3 kg/m^2 STANDARD_DEVIATION 3.8 • n=5 Participants	27.8 kg/m^2 STANDARD_DEVIATION 3.7 • n=7 Participants	28.1 kg/m^2 STANDARD_DEVIATION 3.7 • n=5 Participants
Hemoglobin A1c	5.6 Percentage of glycated hemoglobin STANDARD_DEVIATION 0.4 • n=5 Participants	5.5 Percentage of glycated hemoglobin STANDARD_DEVIATION 0.3 • n=7 Participants	5.5 Percentage of glycated hemoglobin STANDARD_DEVIATION 0.3 • n=5 Participants
Number of participants homozygous for major alleles of both GCGR and GIPR	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Number of participants homozygous for p.G40S allele of GCGR	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Number of participants homozygous for p.E354Q allele of GIPR	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: 0-10 minutes

Population: The analysis population included 52 patients who completed the study and for whom the necessary blood samples were collected and available for assays of insulin and glucose.

The ratio of the area-under-the-curve (AUC) for 1st phase insulin secretion in the exenatide-stimulated FSIGT divided by the AUC for 1st phase insulin secretion in the saline FSIGT.

Outcome measures

Measure	Exenatide First Followed by Saline n=26 Participants Participants who were randomized to undergo exenatide-stimulated FSIGT first followed by saline FSIGT	Saline First Followed by Exenatide n=26 Participants Participants who were randomized to undergo the saline FSIGT followed by the exenatide-stimulated FSIGT	Homozygotes for the p.E354Q Allele of GIPR Participants with two copies of the p.E354Q allele of the GIPR gene
Exenatide Effect on First Phase Insulin Secretion	1.90 Ratio (no units) Standard Error 0.17	2.18 Ratio (no units) Standard Error 0.25	—

PRIMARY outcome

Timeframe: 25-50 minutes

Population: The analysis population included 52 patients who completed the study and for whom the necessary blood samples were collected and available for assays of insulin and glucose.

The ratio of the glucose disappearance rate (exenatide) divided by the glucose disappearance rate (placebo).

Glucose disappearance rates were calculated as the slope of the plot of the logarithm of the glucose concentration as a function of time.

Outcome measures

Measure	Exenatide First Followed by Saline n=26 Participants Participants who were randomized to undergo exenatide-stimulated FSIGT first followed by saline FSIGT	Saline First Followed by Exenatide n=26 Participants Participants who were randomized to undergo the saline FSIGT followed by the exenatide-stimulated FSIGT	Homozygotes for the p.E354Q Allele of GIPR Participants with two copies of the p.E354Q allele of the GIPR gene
Exenatide Effect on Glucose Disappearance Rate	2.16 Ratio (no units) Standard Error 0.19	2.28 Ratio (no units) Standard Error 0.20	—

SECONDARY outcome

Timeframe: 25-50 minutes

Population: The analysis population included 52 patients who completed the study and for whom the necessary blood samples were collected and available for assays of insulin and glucose.

The slope of the line plotting the logarithm of glucose concentrations as a function of time during the exenatide frequently sampled intravenous glucose tolerance test. The slope of the line was estimated as the slope of the least-squares fit to the data points between 25-50 minutes.

Outcome measures

Measure	Exenatide First Followed by Saline n=26 Participants Participants who were randomized to undergo exenatide-stimulated FSIGT first followed by saline FSIGT	Saline First Followed by Exenatide n=26 Participants Participants who were randomized to undergo the saline FSIGT followed by the exenatide-stimulated FSIGT	Homozygotes for the p.E354Q Allele of GIPR Participants with two copies of the p.E354Q allele of the GIPR gene
Glucose Disappearance Rate (Exenatide)	1056 Log(mg/dL) per min Standard Error 94	1131 Log(mg/dL) per min Standard Error 81	—

SECONDARY outcome

Timeframe: 25-50 minutes

Population: The analysis population included 52 patients who completed the study and for whom the necessary blood samples were collected and available for assays of insulin and glucose.

The slope of the line plotting the logarithm of glucose concentrations as a function of time during the placebo frequently sampled intravenous glucose tolerance test. The slope of the line was estimated as the slope of the least-squares fit to the data points between 25-50 minutes.

Outcome measures

Measure	Exenatide First Followed by Saline n=26 Participants Participants who were randomized to undergo exenatide-stimulated FSIGT first followed by saline FSIGT	Saline First Followed by Exenatide n=26 Participants Participants who were randomized to undergo the saline FSIGT followed by the exenatide-stimulated FSIGT	Homozygotes for the p.E354Q Allele of GIPR Participants with two copies of the p.E354Q allele of the GIPR gene
Glucose Disappearance Rate (Placebo)	500 Log(mg/dL) per min Standard Error 37	547 Log(mg/dL) per min Standard Error 48	—

SECONDARY outcome

Timeframe: 0-10 minutes

Population: The analysis population included 52 patients who completed the study and for whom the necessary blood samples were collected and available for assays of insulin and glucose.

The area under the curve for plasma insulin levels during a frequently sampled intravenous glucose tolerance test after participants received exenatide

Outcome measures

Measure	Exenatide First Followed by Saline n=26 Participants Participants who were randomized to undergo exenatide-stimulated FSIGT first followed by saline FSIGT	Saline First Followed by Exenatide n=26 Participants Participants who were randomized to undergo the saline FSIGT followed by the exenatide-stimulated FSIGT	Homozygotes for the p.E354Q Allele of GIPR Participants with two copies of the p.E354Q allele of the GIPR gene
First Phase Insulin Secretion (Exenatide)	561 microunits/mL*min Standard Error 94	494 microunits/mL*min Standard Error 50	—

SECONDARY outcome

Timeframe: 0-10 minutes

Population: The analysis population included 52 patients who completed the study and for whom the necessary blood samples were collected and available for assays of insulin and glucose.

The area under the curve for plasma insulin levels during a frequently sampled intravenous glucose tolerance test after participants received saline

Outcome measures

Measure	Exenatide First Followed by Saline n=26 Participants Participants who were randomized to undergo exenatide-stimulated FSIGT first followed by saline FSIGT	Saline First Followed by Exenatide n=26 Participants Participants who were randomized to undergo the saline FSIGT followed by the exenatide-stimulated FSIGT	Homozygotes for the p.E354Q Allele of GIPR Participants with two copies of the p.E354Q allele of the GIPR gene
First Phase Insulin Secretion (Placebo)	305 microunits/mL*min Standard Error 38	254 microunits/mL*min Standard Error 23	—

SECONDARY outcome

Timeframe: 0 - 10 min during the FSIGT

Population: Participants with the specified genotypes. Based on the observation that the order of FSIGT (exenatide-first versus saline-first) did not affect the data obtained in the FSIGT, we have pooled data from the two arms of the study (exenatide-first and saline-first).

The effect of exenatide to increase first-phase insulin secretion was defined as the ratio of area-under-the-curve (AUC) for insulin levels during the first 10 minutes of the exenatide-stimulated FSIGT divided by the AUC for first phase insulin secretion during the saline FSIGT..

Outcome measures

Measure	Exenatide First Followed by Saline n=19 Participants Participants who were randomized to undergo exenatide-stimulated FSIGT first followed by saline FSIGT	Saline First Followed by Exenatide n=20 Participants Participants who were randomized to undergo the saline FSIGT followed by the exenatide-stimulated FSIGT	Homozygotes for the p.E354Q Allele of GIPR n=13 Participants Participants with two copies of the p.E354Q allele of the GIPR gene
Drug Effect on First-Phase Insulin Secretion (Genotype-specific)	2.25 Ratio: no units Standard Error 0.31	1.94 Ratio: no units Standard Error 0.21	1.87 Ratio: no units Standard Error 0.27

SECONDARY outcome

Timeframe: 25-50 min during the FSIGT

Population: Same as for effect of exenatide on first phase insulin secretion

The rate of glucose disappearance was calculated as the slope of a least-squared line fitted to the logarithms of glucose concentrations during time 25-50 min of FSIGTs

Outcome measures

Measure	Exenatide First Followed by Saline n=19 Participants Participants who were randomized to undergo exenatide-stimulated FSIGT first followed by saline FSIGT	Saline First Followed by Exenatide n=20 Participants Participants who were randomized to undergo the saline FSIGT followed by the exenatide-stimulated FSIGT	Homozygotes for the p.E354Q Allele of GIPR n=13 Participants Participants with two copies of the p.E354Q allele of the GIPR gene
Exenatide's Effect on the Rate of Glucose-disappearance (Genotype Specific)	2.19 Log(mg/dL) per min Standard Error 0.24	2.28 Log(mg/dL) per min Standard Error 0.24	2.18 Log(mg/dL) per min Standard Error 0.19

Adverse Events

Total Study Population (Control Study)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Total Study Population (Exenatide Study)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Total Study Population (Control Study) n=62 participants at risk The analysis is based on observations during the control studies in the 62 individuals who completed the control intravenous glucose tolerance testing. We report the adverse events separately for the control studies versus the exenatide studies because the literature documents the fact that GLP1R agonists like exenatide frequently induce nausea and/or vomiting.	Total Study Population (Exenatide Study) n=62 participants at risk The analysis is based on observations during the control studies in the 62 individuals who completed exenatide intravenous glucose tolerance testing. We report the adverse events separately for the control studies versus the exenatide studies because the literature documents the fact that GLP1R agonists like exenatide frequently induce nausea and/or vomiting.
Gastrointestinal disorders Nausea or vomiting	1.6% 1/62 • Number of events 1 • Adverse events were assessed during the time (one day) participants were in the clinic for the frequently sampled intravenous glucose tolerance test Participants were interviewed by nursing staff on the day of the frequently sampled intravenous glucose tolerance test.	4.8% 3/62 • Number of events 3 • Adverse events were assessed during the time (one day) participants were in the clinic for the frequently sampled intravenous glucose tolerance test Participants were interviewed by nursing staff on the day of the frequently sampled intravenous glucose tolerance test.
Vascular disorders Headache	3.2% 2/62 • Number of events 2 • Adverse events were assessed during the time (one day) participants were in the clinic for the frequently sampled intravenous glucose tolerance test Participants were interviewed by nursing staff on the day of the frequently sampled intravenous glucose tolerance test.	6.5% 4/62 • Number of events 4 • Adverse events were assessed during the time (one day) participants were in the clinic for the frequently sampled intravenous glucose tolerance test Participants were interviewed by nursing staff on the day of the frequently sampled intravenous glucose tolerance test.

Additional Information

Simeon Taylor, MD, PhD (Professor of Medicine0

University of Maryland School of Medicine

Phone: 4107066439

Email: staylor2@som.umaryland.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place