Cardiovascular Effects of GLP-1 Receptor Activation
Sponsor
Vanderbilt University Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT03101930
Collaborator
American Heart Association (Other)
329
1
3
49.8
6.6
Study Details
Study Description
Brief Summary
This project tests the principle hypothesis that stable glucagon like peptide-1 (GLP-1) analogues have specific GLP1R-dependent beneficial effects on vascular endothelial function, fibrinolysis and inflammation in obesity that exceed the benefits of weight loss, and that genetic or other individual factors that modulate GLP1R sensitivity can modify the effect of these analogues on cardiovascular risk.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
329 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Treatment with liraglutide or sitagliptin will be masked using matching placebo.
Primary Purpose:
Basic Science
Official Title:
Cardiovascular Effects of GLP-1 Receptor Activation
Actual Study Start Date
:
May 1, 2017
Actual Primary Completion Date
:
Jun 24, 2021
Actual Study Completion Date
:
Jun 24, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: liraglutide Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. |
Drug: Liraglutide
subcutaneous liraglutide daily
Drug: Placebos
Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39.
Drug: Exendin (9-39)
All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment.
|
| Active Comparator: sitagliptin Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. |
Drug: Sitagliptin
oral sitagliptin daily
Drug: Placebos
Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39.
Drug: Exendin (9-39)
All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment.
|
| Active Comparator: hypocaloric diet Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. |
Other: hypocaloric diet
Reduced calorie intake to achieve weight loss.
Drug: Placebos
Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39.
Drug: Exendin (9-39)
All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment.
|
Outcome Measures
Primary Outcome Measures
- Change in Flow-mediated Dilation [Baseline to 14 weeks]
Brachial artery diameter is measured under basal conditions and during reactive hyperemia (Flow Mediated Dilation as %)
- Urine Albumin-to-creatinine Ratio [Baseline to 13 weeks]
Ratio of urine albumin to creatinine in a spot urine collected after overnight rest
- Change in Plasminogen Activator Inhibitor-1 [Baseline to 14 weeks]
Plasma plasminogen activator inhibitor-1 antigen
Secondary Outcome Measures
- Blood Pressure [After 2 weeks and 14 weeks of treatment]
The mean of three systolic blood pressure measurements one minute apart using a oscillometric recording device with patient in supine position
- Heart Rate [After 2 weeks and 14 weeks of treatment]
The mean of three measurements with the patient in the supine position
- Fasting Glucose [After 2 weeks and 14 weeks of treatment]
Blood glucose collected after overnight fast
- Fasting Insulin [After 2 weeks and 14 weeks of treatment]
Plasma insulin collected after overnight fast
Other Outcome Measures
- Change in Weight [Change from baseline to 14 weeks]
Weight measured in light clothing without shoes
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Men and women,
-
Age 18 to 65 years, and
-
FPG (100-125 mg/dL) or, IGT (two-hour plasma glucose 140-199 mg/dL) or, HbA1C 5.7-6.4%
-
BMI≥30 kg/M2
-
The ability to provide informed consent before any trial-related activities.
Exclusion Criteria:
-
Diabetes type 1 or type 2, as defined by a FPG of 126 mg/dL or greater, a two-hour plasma glucose of 200 mg/dL or greater, or the use of anti-diabetic medication
-
Resistant hypertension, defined as hypertension requiring the administration of more than three anti-hypertensive agents including a diuretic to achieve control
-
Use of spironolactone
-
Known or suspected allergy to trial medications, excipients, or related products.
-
Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma
-
Personal history of non-familial medullary thyroid carcinoma
-
History of pancreatitis
-
Contraindications to study medications, worded specifically as stated in the product's prescribing information
-
Pregnancy or breast-feeding. Women of child-bearing potential will be required to have undergone tubal ligation or to be using an oral contraceptive or barrier methods of birth control
-
Subjects who have participated in a weight-reduction program during the last six month or whose weight has increased or decreased more than two kg over the preceding six months
-
Cardiovascular disease such as myocardial infarction within six months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (left ventricular hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
-
Treatment with anticoagulants
-
History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack
-
History or presence of immunological or hematological disorders
-
Diagnosis of asthma requiring regular inhaler use
-
Clinically significant gastrointestinal impairment that could interfere with drug absorption
-
Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino transaminase [ALT] >3.0 x upper limit of normal range)
-
Individuals with an eGFR<30 mL/min/1.73 m2 or with a UACR >1000µg/mg, where eGFR is determined by the four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum creatinine is expressed in mg/dL and age in years: eGFR (mL/min/1.73m2)=186 • Scr-1.154 • age-0.203 • (1.212 if black) • (0.742 if female)
-
Hematocrit <35%
-
Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
-
Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
-
Treatment with lithium salts
-
History of alcohol or drug abuse
-
Treatment with any investigational drug in the one month preceding the study
-
Previous randomization in this trial
-
Mental conditions rendering a subject unable to understand the nature, scope and possible consequences of the study
-
Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
Sponsors and Collaborators
- Vanderbilt University Medical Center
- American Heart Association
Investigators
- Principal Investigator: James M. Luther, M.D., Vanderbilt University Medical Center
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
James Matt Luther,
Associate Professor of Medicine and Pharmacology,
Vanderbilt University Medical Center
ClinicalTrials.gov Identifier:
NCT03101930
Other Study ID Numbers:
- IRB# 170213
First Posted:
Apr 5, 2017
Last Update Posted:
Aug 16, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | CONSORT flow details: 329 signed consent. 178 individuals did not meet inclusion/exclusion criteria. 35 individuals declined to participate. 23 individuals did not return for subsequent visits. 93 individuals randomized. 88 individuals completed study days. |
| Arm/Group Title | Liraglutide | Sitagliptin | Hypocaloric Diet |
|---|---|---|---|
| Arm/Group Description | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Liraglutide: subcutaneous liraglutide daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| Period Title: Overall Study | |||
| STARTED | 46 | 23 | 24 |
| COMPLETED | 44 | 22 | 22 |
| NOT COMPLETED | 2 | 1 | 2 |
Baseline Characteristics
| Arm/Group Title | Liraglutide | Sitagliptin | Hypocaloric Diet | Total |
|---|---|---|---|---|
| Arm/Group Description | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Liraglutide: subcutaneous liraglutide daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Total of all reporting groups |
| Overall Participants | 46 | 23 | 24 | 93 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
49.8
(9.9)
|
52.8
(10.5)
|
48.9
(12.1)
|
50.3
(10.6)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
33
71.7%
|
16
69.6%
|
14
58.3%
|
63
67.7%
|
| Male |
13
28.3%
|
7
30.4%
|
10
41.7%
|
30
32.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
1
2.2%
|
2
8.7%
|
1
4.2%
|
4
4.3%
|
| Not Hispanic or Latino |
44
95.7%
|
21
91.3%
|
23
95.8%
|
88
94.6%
|
| Unknown or Not Reported |
1
2.2%
|
0
0%
|
0
0%
|
1
1.1%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
3
6.5%
|
0
0%
|
0
0%
|
3
3.2%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
5
10.9%
|
4
17.4%
|
4
16.7%
|
13
14%
|
| White |
38
82.6%
|
18
78.3%
|
19
79.2%
|
75
80.6%
|
| More than one race |
0
0%
|
1
4.3%
|
1
4.2%
|
2
2.2%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
46
100%
|
23
100%
|
24
100%
|
93
100%
|
| Flow mediated dilation (Percentage) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Percentage] |
10.5
(5.2)
|
10.4
(5.37)
|
10.2
(5.3)
|
10.4
(5.2)
|
| Urine Albumin-Creatinine ratio (mg/g) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [mg/g] |
12.04
(23.6)
|
7.85
(7.6)
|
6.3
(3.8)
|
9.6
(17.3)
|
| Plasminogen Activator Inhibitor-1, plasma (U/mL) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [U/mL] |
20.2
(9.2)
|
18.5
(8.6)
|
18.5
(8.0)
|
19.4
(8.7)
|
Outcome Measures
| Title | Change in Flow-mediated Dilation |
|---|---|
| Description | Brachial artery diameter is measured under basal conditions and during reactive hyperemia (Flow Mediated Dilation as %) |
| Time Frame | Baseline to 14 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Incomplete data due to missed study visits and missing samples in the following time periods/arms (n= number of participants with missing data): Liraglutide/Placebo: Week 2 (n=5); Week 14 (n=4) Liraglutide/Exendin: Week 2 (n=11); Week 14 (n=12) Sitagliptin/Placebo: Week 2 (n=2) Sitagliptin/Exendin: Week 2 (n=3); Week 14 (n=2) Diet/Placebo: Week 2 (n=1); Week 14 (n=6) Diet/Exendin: Week 2 (n=7); Week 14 (n=11) |
| Arm/Group Title | Liraglutide | Sitagliptin | Hypocaloric Diet |
|---|---|---|---|
| Arm/Group Description | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Liraglutide: subcutaneous liraglutide daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| Measure Participants | 44 | 22 | 22 |
| Baseline to 2 weeks (Placebo infusion) |
0.71
(4.82)
|
2.06
(6.42)
|
1.24
(5.09)
|
| Baseline to 2 weeks (Exendin infusion) |
0.48
(5.81)
|
0.13
(4.49)
|
1.43
(7.09)
|
| Baseline to 14 weeks (Placebo infusion) |
1.43
(5.33)
|
1.59
(5.74)
|
1.01
(5.38)
|
| Baseline to 14 weeks (Exendin infusion) |
1.73
(5.22)
|
1.42
(5.88)
|
0.42
(4.28)
|
| Title | Urine Albumin-to-creatinine Ratio |
|---|---|
| Description | Ratio of urine albumin to creatinine in a spot urine collected after overnight rest |
| Time Frame | Baseline to 13 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to missed study visits and missing samples, there is incomplete data for the following arms/time periods: Liraglutide: 2 participants; Diet: 6 participants |
| Arm/Group Title | Liraglutide | Sitagliptin | Hypocaloric Diet |
|---|---|---|---|
| Arm/Group Description | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Liraglutide: subcutaneous liraglutide daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| Measure Participants | 44 | 22 | 22 |
| Baseline |
12.0
(23.6)
|
7.9
(7.6)
|
6.3
(3.8)
|
| 13 Weeks |
10.5
(14.8)
|
9.2
(10.7)
|
10.1
(19.4)
|
| Title | Change in Plasminogen Activator Inhibitor-1 |
|---|---|
| Description | Plasma plasminogen activator inhibitor-1 antigen |
| Time Frame | Baseline to 14 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to missed study visits and missing samples, there is incomplete data for the following arms/time periods: Liraglutide: Baseline: 2 participants/Week 14: 3 participants; Sitagliptin: Baseline: 1 participants/Week 14: 1 participants; Diet: Baseline: 3 participants/Week 14: 6 participants |
| Arm/Group Title | Liraglutide | Sitagliptin | Hypocaloric Diet |
|---|---|---|---|
| Arm/Group Description | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Liraglutide: subcutaneous liraglutide daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| Measure Participants | 44 | 22 | 22 |
| Baseline to 2 weeks |
-2.4
(7.8)
|
-1.3
(8.3)
|
1.1
(6.9)
|
| Baseline to 14 weeks |
-3.7
(8.7)
|
1.3
(6.3)
|
-3.6
(6.6)
|
| Title | Blood Pressure |
|---|---|
| Description | The mean of three systolic blood pressure measurements one minute apart using a oscillometric recording device with patient in supine position |
| Time Frame | After 2 weeks and 14 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to missed study visits there is incomplete data for the following arms/time periods: Liraglutide 14 weeks- 2 participants; Diet 14 weeks: 5 participants |
| Arm/Group Title | Liraglutide | Sitagliptin | Hypocaloric Diet |
|---|---|---|---|
| Arm/Group Description | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Liraglutide: subcutaneous liraglutide daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| Measure Participants | 44 | 22 | 22 |
| Baseline |
124.1
(7.7)
|
120.2
(11.3)
|
127.7
(8.3)
|
| 2 weeks |
122.9
(6.3)
|
117.5
(11.3)
|
121.7
(6.8)
|
| 14 weeks |
122.2
(7.8)
|
118.2
(13.9)
|
119.7
(11.1)
|
| Title | Heart Rate |
|---|---|
| Description | The mean of three measurements with the patient in the supine position |
| Time Frame | After 2 weeks and 14 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to missed study visits there is incomplete data for the following arms/time periods: Liraglutide 14 weeks- 2 participants; Diet 14 weeks: 5 participants |
| Arm/Group Title | Liraglutide | Sitagliptin | Hypocaloric Diet |
|---|---|---|---|
| Arm/Group Description | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Liraglutide: subcutaneous liraglutide daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| Measure Participants | 44 | 22 | 22 |
| Baseline |
64.9
(7.5)
|
67.2
(9.0)
|
63.8
(8.8)
|
| 2 weeks |
68.9
(6.4)
|
66.2
(9.2)
|
63.2
(9.5)
|
| 14 weeks |
68.9
(5.6)
|
65.9
(8.5)
|
61.7
(7.9)
|
| Title | Fasting Glucose |
|---|---|
| Description | Blood glucose collected after overnight fast |
| Time Frame | After 2 weeks and 14 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to missed study visits there is incomplete data for the following arms/time periods: Liraglutide Baseline-1, 2 weeks 1, 14 weeks- 2 participants; Sitagliptin 2 weeks 1, 14 weeks- 1 participants; Diet 14 weeks: 5 participants |
| Arm/Group Title | Liraglutide | Sitagliptin | Hypocaloric Diet |
|---|---|---|---|
| Arm/Group Description | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Liraglutide: subcutaneous liraglutide daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| Measure Participants | 44 | 22 | 22 |
| Baseline |
95.3
(8.6)
|
97.6
(10.0)
|
94.5
(12.0)
|
| 2 weeks |
84.26
(7.9)
|
93.9
(8.1)
|
92.4
(11.3)
|
| 14 weeks |
85.2
(7.3)
|
96.6
(5.6)
|
91.2
(9.8)
|
| Title | Fasting Insulin |
|---|---|
| Description | Plasma insulin collected after overnight fast |
| Time Frame | After 2 weeks and 14 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to missed study visits or missing data there is incomplete data for the following arms/time periods: Liraglutide 2 weeks 3, 14 weeks- 3 participants; Sitagliptin 2 weeks 2, 14 weeks- 1 participants; Diet 14 weeks: 5 participants |
| Arm/Group Title | Liraglutide | Sitagliptin | Hypocaloric Diet |
|---|---|---|---|
| Arm/Group Description | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Liraglutide: subcutaneous liraglutide daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| Measure Participants | 44 | 22 | 22 |
| Baseline |
22.7
(16.8)
|
23.3
(14.4)
|
26.7
(21.2)
|
| 2 weeks |
18.3
(12.5)
|
29.4
(25.4)
|
19.7
(16.5)
|
| 14 weeks |
20.3
(14.7)
|
26.0
(19.0)
|
20.3
(13.7)
|
| Title | Change in Weight |
|---|---|
| Description | Weight measured in light clothing without shoes |
| Time Frame | Change from baseline to 14 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to missed study visits or missing data there is incomplete data for the following arms/time periods: Liraglutide 2 participants; Diet 5 participants |
| Arm/Group Title | Liraglutide | Sitagliptin | Hypocaloric Diet |
|---|---|---|---|
| Arm/Group Description | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Liraglutide: subcutaneous liraglutide daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. |
| Measure Participants | 42 | 22 | 17 |
| Mean (Standard Deviation) [kg] |
-2.72
(3.44)
|
-0.71
(2.12)
|
-4.95
(3.98)
|
Adverse Events
| Time Frame | After randomization to 14 weeks | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse event information was collected for any untoward or unfavorable medical occurrence in a participant, including any abnormal sign, symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research. Adverse events were collected from the time of randomization through participant completion at each screening visit, study day, and at week 4, week 8 and week 12 check-ins. | |||||
| Arm/Group Title | Liraglutide | Sitagliptin | Hypocaloric Diet | |||
| Arm/Group Description | Subjects in the liraglutide group will receive subcutaneous liraglutide (0.6 mg/d for one week, 1.2 mg/d for one week, and then 1.8 mg/d for 12 weeks) and oral placebo. Liraglutide: subcutaneous liraglutide daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the sitagliptin group will receive subcutaneous placebo daily and sitagliptin 100 mg/d orally for 14 weeks. Sitagliptin: oral sitagliptin daily Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | Subjects in the hypocaloric diet group will be given a caloric goal designed to achieve a weight loss similar to that expected in the liraglutide treatment arm based on his or her resting energy expenditure. Subjects will be provided counseling and written instructions on how to achieve their daily caloric goal, including use of their own mobile phone applications to monitor caloric intake. To assure compliance with the prescribed caloric goal, subjects will meet with the study dietitian every other week for problem solving and review of diet intake logs. hypocaloric diet: Reduced calorie intake to achieve weight loss. Placebos: Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39. Exendin (9-39): All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment. | |||
All Cause Mortality |
||||||
| Liraglutide | Sitagliptin | Hypocaloric Diet | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/46 (0%) | 0/23 (0%) | 0/24 (0%) | |||
Serious Adverse Events |
||||||
| Liraglutide | Sitagliptin | Hypocaloric Diet | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/46 (0%) | 1/23 (4.3%) | 1/24 (4.2%) | |||
| Gastrointestinal disorders | ||||||
| Diverticulitis | 0/46 (0%) | 0 | 0/23 (0%) | 0 | 1/24 (4.2%) | 1 |
| Renal and urinary disorders | ||||||
| Nephrolithiasis and hydronephrosis | 0/46 (0%) | 0 | 1/23 (4.3%) | 1 | 0/24 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Cellulitis/abscess | 0/46 (0%) | 0 | 1/23 (4.3%) | 1 | 0/24 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Liraglutide | Sitagliptin | Hypocaloric Diet | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 26/46 (56.5%) | 6/23 (26.1%) | 6/24 (25%) | |||
| Cardiac disorders | ||||||
| Bradycardia | 0/46 (0%) | 0 | 0/23 (0%) | 0 | 1/24 (4.2%) | 1 |
| Gastrointestinal disorders | ||||||
| Nausea | 8/46 (17.4%) | 8 | 0/23 (0%) | 0 | 1/24 (4.2%) | 1 |
| Diarrhea | 3/46 (6.5%) | 3 | 0/23 (0%) | 0 | 0/24 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Injury | 2/46 (4.3%) | 2 | 0/23 (0%) | 0 | 0/24 (0%) | 0 |
| Nervous system disorders | ||||||
| Headache | 4/46 (8.7%) | 4 | 0/23 (0%) | 0 | 0/24 (0%) | 0 |
| Lightheaded | 2/46 (4.3%) | 2 | 0/23 (0%) | 0 | 1/24 (4.2%) | 1 |
| Insomnia | 1/46 (2.2%) | 1 | 0/23 (0%) | 0 | 0/24 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Upper respiratory tract infection | 3/46 (6.5%) | 3 | 0/23 (0%) | 0 | 0/24 (0%) | 0 |
| Surgical and medical procedures | ||||||
| Study day procedure adverse event | 22/46 (47.8%) | 41 | 6/23 (26.1%) | 9 | 6/24 (25%) | 9 |
Limitations/Caveats
Study enrollment and conduct interrupted due to COVID-19 pandemic. Exendin not available for all study participants.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. James M. Luther, MD MSCI (Principal Investigator) |
|---|---|
| Organization | Vanderbilt University Medical Center |
| Phone | (615) 936-3420 |
| james.luther@vumc.org |
Responsible Party:
James Matt Luther,
Associate Professor of Medicine and Pharmacology,
Vanderbilt University Medical Center
ClinicalTrials.gov Identifier:
NCT03101930
Other Study ID Numbers:
- IRB# 170213
First Posted:
Apr 5, 2017
Last Update Posted:
Aug 16, 2022
Last Verified:
Jul 1, 2022