Trial Outcomes & Findings for GLP-1 Therapy: The Role of IL-6 Signaling and Adipose Tissue Remodeling in Metabolic Response (NCT NCT04387201)

NCT ID: NCT04387201

Last Updated: 2024-12-05

Results Overview

natural log transformed data is reported

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

23 participants

Primary outcome timeframe

6 weeks after start of each intervention

Results posted on

2024-12-05

Participant Flow

Participant milestones

Participant milestones
Measure
Cyanocobalamin, Then Dulaglutide
Participants first received Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks. After a washout period of 3 weeks, they then received Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks. Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
Dulaglutide, Then Cyanocobalamin
Participants first received Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks. After a washout period of of 3 weeks, they then Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks. Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks. Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
First Intervention (6 Weeks)
STARTED
17
6
First Intervention (6 Weeks)
Received Intervention
16
6
First Intervention (6 Weeks)
COMPLETED
12
6
First Intervention (6 Weeks)
NOT COMPLETED
5
0
Washout (3 Weeks)
STARTED
12
6
Washout (3 Weeks)
COMPLETED
12
6
Washout (3 Weeks)
NOT COMPLETED
0
0
Second Intervention (6 Weeks)
STARTED
12
6
Second Intervention (6 Weeks)
Received Intervention
12
6
Second Intervention (6 Weeks)
COMPLETED
11
4
Second Intervention (6 Weeks)
NOT COMPLETED
1
2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

GLP-1 Therapy: The Role of IL-6 Signaling and Adipose Tissue Remodeling in Metabolic Response

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Cyanocobalamin, Then Dulaglutide
n=17 Participants
Participants first received Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks. After a washout period of 3 weeks, they then received Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks. Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
Dulaglutide, Then Cyanocobalamin
n=6 Participants
Participants first received Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks. After a washout period of of 3 weeks, they then Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks. Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks. Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
Total
n=23 Participants
Total of all reporting groups
Age, Continuous
40 years
STANDARD_DEVIATION 7 • n=5 Participants
39 years
STANDARD_DEVIATION 5 • n=7 Participants
39 years
STANDARD_DEVIATION 6 • n=5 Participants
Sex: Female, Male
Female
9 Participants
n=5 Participants
5 Participants
n=7 Participants
14 Participants
n=5 Participants
Sex: Female, Male
Male
8 Participants
n=5 Participants
1 Participants
n=7 Participants
9 Participants
n=5 Participants
Race/Ethnicity, Customized
Caucasian
1 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
Race/Ethnicity, Customized
Black
5 Participants
n=5 Participants
3 Participants
n=7 Participants
8 Participants
n=5 Participants
Race/Ethnicity, Customized
Hispanic
8 Participants
n=5 Participants
0 Participants
n=7 Participants
8 Participants
n=5 Participants
Race/Ethnicity, Customized
Other
3 Participants
n=5 Participants
2 Participants
n=7 Participants
5 Participants
n=5 Participants
Region of Enrollment
United States
17 participants
n=5 Participants
6 participants
n=7 Participants
23 participants
n=5 Participants
Body Mass Index
30.5 kilograms per square meter
STANDARD_DEVIATION 3.4 • n=5 Participants
31.4 kilograms per square meter
STANDARD_DEVIATION 2.8 • n=7 Participants
30.73 kilograms per square meter
STANDARD_DEVIATION 3.26 • n=5 Participants
Systolic Blood Pressure
126 millimeters of mercury
STANDARD_DEVIATION 13 • n=5 Participants
118 millimeters of mercury
STANDARD_DEVIATION 11 • n=7 Participants
123 millimeters of mercury
STANDARD_DEVIATION 12 • n=5 Participants
Diastolic Blood Pressure
79 millimeters of mercury
STANDARD_DEVIATION 6 • n=5 Participants
75 millimeters of mercury
STANDARD_DEVIATION 8 • n=7 Participants
77 millimeters of mercury
STANDARD_DEVIATION 6 • n=5 Participants
Fasting Glucose Level
94 milligrams per deciliter
STANDARD_DEVIATION 16 • n=5 Participants
96 milligrams per deciliter
STANDARD_DEVIATION 14 • n=7 Participants
94 milligrams per deciliter
STANDARD_DEVIATION 15 • n=5 Participants
percentage of glycosylated hemoglobin
5.5 percentage of glycosylated hemoglobin"
STANDARD_DEVIATION 0.3 • n=5 Participants
5.7 percentage of glycosylated hemoglobin"
STANDARD_DEVIATION 0.1 • n=7 Participants
5.5 percentage of glycosylated hemoglobin"
STANDARD_DEVIATION 0.2 • n=5 Participants
Triglycerides Level
135 milligrams per deciliter
STANDARD_DEVIATION 93 • n=5 Participants
124 milligrams per deciliter
STANDARD_DEVIATION 86 • n=7 Participants
132 milligrams per deciliter
STANDARD_DEVIATION 91 • n=5 Participants
Total Cholesterol Level
193 milligrams per deciliter
STANDARD_DEVIATION 38 • n=5 Participants
201 milligrams per deciliter
STANDARD_DEVIATION 31 • n=7 Participants
195 milligrams per deciliter
STANDARD_DEVIATION 36 • n=5 Participants
high-density lipoprotein (HDL) Cholesterol Level
56 milligrams per deciliter
STANDARD_DEVIATION 24 • n=5 Participants
55 milligrams per deciliter
STANDARD_DEVIATION 8 • n=7 Participants
55 milligrams per deciliter
STANDARD_DEVIATION 21 • n=5 Participants
low-density lipoprotein (LDL) Cholesterol Level
111 milligrams per deciliter
STANDARD_DEVIATION 35 • n=5 Participants
122 milligrams per deciliter
STANDARD_DEVIATION 28 • n=7 Participants
113 milligrams per deciliter
STANDARD_DEVIATION 33 • n=5 Participants
aspartate aminotransferase (AST) Level
22 units per liter
STANDARD_DEVIATION 8 • n=5 Participants
19 units per liter
STANDARD_DEVIATION 5 • n=7 Participants
21 units per liter
STANDARD_DEVIATION 7 • n=5 Participants
alanine aminotransferase (ALT) Level
24 units per liter
STANDARD_DEVIATION 14 • n=5 Participants
20 units per liter
STANDARD_DEVIATION 10 • n=7 Participants
22 units per liter
STANDARD_DEVIATION 13 • n=5 Participants
Creatinine Level
0.9 milligrams per deciliter
STANDARD_DEVIATION 0.3 • n=5 Participants
0.9 milligrams per deciliter
STANDARD_DEVIATION 0.2 • n=7 Participants
0.9 milligrams per deciliter
STANDARD_DEVIATION 0.2 • n=5 Participants
Hemoglobin Level
14 grams per deciliter
STANDARD_DEVIATION 2 • n=5 Participants
13 grams per deciliter
STANDARD_DEVIATION 2 • n=7 Participants
13 grams per deciliter
STANDARD_DEVIATION 2 • n=5 Participants
Platelets Count
296 billion cells per liter
STANDARD_DEVIATION 90 • n=5 Participants
285 billion cells per liter
STANDARD_DEVIATION 51 • n=7 Participants
293 billion cells per liter
STANDARD_DEVIATION 82 • n=5 Participants
thyroid-stimulating hormone (TSH) level
1.8 milli-international units per liter
STANDARD_DEVIATION 1.4 • n=5 Participants
1.8 milli-international units per liter
STANDARD_DEVIATION 0.7 • n=7 Participants
1.8 milli-international units per liter
STANDARD_DEVIATION 1.2 • n=5 Participants
Vitamin B12 Level
497 picograms per milliliter
STANDARD_DEVIATION 178 • n=5 Participants
495 picograms per milliliter
STANDARD_DEVIATION 255 • n=7 Participants
496 picograms per milliliter
STANDARD_DEVIATION 199 • n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks after start of each intervention

natural log transformed data is reported

Outcome measures

Outcome measures
Measure
Cyanocobalamin
n=18 Participants
Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks.
Dulaglutide
n=18 Participants
Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
Cytokine Interleukin-6 (IL-6) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue)
7.88 natural log(arbitrary units)
Interval 7.16 to 8.6
7.67 natural log(arbitrary units)
Interval 6.98 to 8.35

PRIMARY outcome

Timeframe: 6 weeks after start of each intervention

Uncoupling protein 1 (UCP1) is a marker of beige/brown fat. natural log transformed data is reported

Outcome measures

Outcome measures
Measure
Cyanocobalamin
n=18 Participants
Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks.
Dulaglutide
n=18 Participants
Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
Uncoupling Protein 1 (UCP1) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue)
1.69 natural log(arbitrary units)
Interval -1.26 to 4.63
3.78 natural log(arbitrary units)
Interval 1.68 to 5.87

PRIMARY outcome

Timeframe: 6 weeks after start of each intervention

Population: Data were not collected for this outcome measure.

signaling intermediary with interleukin-6

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

PR domain containing 16 (PRDM16) is a marker of beige/brown fat. natural log transformed data is reported.

Outcome measures

Outcome measures
Measure
Cyanocobalamin
n=18 Participants
Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks.
Dulaglutide
n=18 Participants
Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
PR Domain Containing 16 (PRDM16) Messenger Ribonucleic Acid (mRNA) Level ((From Adipose Tissue)
2.58 natural log(arbitrary units)
Interval 1.47 to 3.69
2.53 natural log(arbitrary units)
Interval 1.48 to 3.58

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Population: Data were not collected for this outcome measure.

marker of beige/brown fat

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Population: Data were not collected for this outcome measure.

marker of beige/brown fat

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Population: Data were not collected for this outcome measure.

marker of beige/brown fat

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Population: Data were not collected for this outcome measure.

marker of beige/brown fat

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Population: Data were not collected for this outcome measure.

signaling intermediary with interleukin-6

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Population: Data were not collected for this outcome measure.

cytokine

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Population: Data were not collected for this outcome measure.

cytokine

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Population: Data were not collected for this outcome measure.

signaling intermediary with interleukin-6

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

natural log transformed data is reported. The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.

Outcome measures

Outcome measures
Measure
Cyanocobalamin
n=18 Participants
Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks.
Dulaglutide
n=18 Participants
Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
Cytokine IL-6 Level (From Plasma)
-0.20 natural log(picograms per milliliter)
Interval -0.93 to 0.53
-0.46 natural log(picograms per milliliter)
Interval -1.15 to 0.22

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Free fatty acids level is a marker for insulin resistance. natural log transformed data is reported The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.

Outcome measures

Outcome measures
Measure
Cyanocobalamin
n=18 Participants
Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks.
Dulaglutide
n=18 Participants
Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
Free Fatty Acids Level (From Plasma)
-5.15 natural log(nanomoles per liter)
Interval -5.76 to -4.55
-5.68 natural log(nanomoles per liter)
Interval -6.22 to -5.14

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Insulin Level is a marker of insulin resistance. natural log transformed data is reported. The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.

Outcome measures

Outcome measures
Measure
Cyanocobalamin
n=18 Participants
Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks.
Dulaglutide
n=18 Participants
Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
Insulin Level (From Plasma)
4.10 natural log(picomoles per liter)
Interval 3.77 to 4.43
3.86 natural log(picomoles per liter)
Interval 3.55 to 4.16

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Glucose Level is a marker of insulin resistance. The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.

Outcome measures

Outcome measures
Measure
Cyanocobalamin
n=18 Participants
Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks.
Dulaglutide
n=18 Participants
Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
Glucose Level (From Plasma)
80.61 milligrams per deciliter
Interval 76.08 to 85.14
78.50 milligrams per deciliter
Interval 74.22 to 82.78

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

natural log transformed data is reported. The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.

Outcome measures

Outcome measures
Measure
Cyanocobalamin
n=18 Participants
Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks.
Dulaglutide
n=18 Participants
Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
Tumor Necrosis Factor - Alpha (From Plasma)
.11 natural log(picograms per milliliter)
Interval -1.22 to 1.45
0.33 natural log(picograms per milliliter)
Interval -0.28 to 0.95

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Population: Data were not collected for this outcome measure.

cytokine

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Population: Data were not collected for this outcome measure.

cytokine

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Population: Data were not collected for this outcome measure.

cytokine

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Population: Data were not collected for this outcome measure.

cytokine

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.

Outcome measures

Outcome measures
Measure
Cyanocobalamin
n=18 Participants
Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks.
Dulaglutide
n=18 Participants
Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
Glucagon-like Peptide-1 (From Plasma)
40.66 picomoles per milliliter
Interval 20.82 to 60.49
206.15 picomoles per milliliter
Interval 187.42 to 224.88

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) is a marker of insulin resistance, calculated according to the formula: fasting insulin (mU/mL) x fasting glucose (mmol/L)/22.5 The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.

Outcome measures

Outcome measures
Measure
Cyanocobalamin
n=18 Participants
Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks.
Dulaglutide
n=18 Participants
Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
2.36 HOMA-IR score
Interval 1.77 to 2.95
1.63 HOMA-IR score
Interval 1.08 to 2.17

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.

Outcome measures

Outcome measures
Measure
Cyanocobalamin
n=18 Participants
Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks.
Dulaglutide
n=18 Participants
Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
Fat Browning Measured as Standard Uptake Value (From Positron Emission Tomography - Computed Tomography (PET-CT) Reading)
Right side PET- CT
0.88 standard uptake value
Interval 0.23 to 1.52
1.37 standard uptake value
Interval 0.48 to 2.27
Fat Browning Measured as Standard Uptake Value (From Positron Emission Tomography - Computed Tomography (PET-CT) Reading)
Left side PET-CT
0.81 standard uptake value
Interval 0.23 to 1.39
1.26 standard uptake value
Interval 0.45 to 2.08

SECONDARY outcome

Timeframe: 6 weeks after start of each intervention

Population: Data were not collected for this outcome measure.

measure of oxygen consumption

Outcome measures

Outcome data not reported

Adverse Events

Cyanocobalamin

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Dulaglutide

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Cyanocobalamin
n=23 participants at risk
Cyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks.
Dulaglutide
n=23 participants at risk
Dulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
General disorders
vasovagal response
4.3%
1/23 • 17 weeks
0.00%
0/23 • 17 weeks

Additional Information

Absalon D Gutierrez, MD

The University of Texas Health Science Center at Houston

Phone: 713-500-6641

Results disclosure agreements

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