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GLP-1 Therapy: The Role of IL-6 Signaling and Adipose Tissue Remodeling in Metabolic Response
Asset
Dulaglutide
Subcutaneous · GLP-1 agonist
Listed sites
1
Recruiting sites
—
Enrollment
23
actual
Study population
Prediabetes / glucose intolerance
Key I/E criteria
•BMI ≤35•HbA1c 5.5-6.4%•eGFR ≥60
Primary endpoints
•Cytokine Interleukin-6 (IL-6) Messenger Ribonucleic Acid (mRNA) Level•Uncoupling Protein 1 (UCP1) Messenger Ribonucleic Acid (mRNA) Level•Signal Transducer and Activator of Transcription 3 (STAT3) Band
Footprint
Where this trial recruits
Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.
Identifiers
Registered as
Timeline
Milestones
Assets
Investigational agents
Study populations
Who this study enrolls
Eligibility
Who can enroll
Inclusion criteria
1. Men and women, ages 18-50 years
2. Diagnosis of Prediabetes - defined as either impaired fasting glucose (fasting glucose of 100-125 mg/dL), impaired glucose tolerance (2-hour postprandial blood glucose of 140-199 mg/dL after 75-gram oral glucose challenge), and/or a hemoglobin A1C ranging from 5.5% to 6.4%.
3. BMI ≤ 35 kg/m2
4. Women of childbearing age must agree to use an acceptable method of pregnancy prevention (barrier methods, abstinence, oral contraception, vaginal rings, long-acting reversible contraceptives, or surgical sterilization) for the duration of the study
5. Patients must have the following laboratory values: Hematocrit ≥ 33 vol%, estimated glomerular filtration rate ≥ 60 mL/min per 1.73 m2, AST (SGOT) < 2.5 times ULN, ALT (SGPT) < 2.5 times ULN, alkaline phosphatase < 2.5 times ULN
6. If patients are receiving antihypertensive medications (other than beta blockers) and/or lipid-lowering medications, they must remain on stable doses for the duration of the study.
7. If patients are receiving NSAIDs or antioxidant vitamins, these must be discontinued one week prior to study initiation and cannot be restarted during the study.
8. If patient takes thyroid medications, these must be dosed to control hypo- or hyperthyroidism.
Exclusion criteria
1. History of Type 1 or Type 2 diabetes mellitus
2. Pregnant or breastfeeding women
3. Medications: Beta blockers, corticosteroids, monoamine oxidase inhibitors, diabetes medications (including incretin mimetics and thiazolidinediones), and/or immunosuppressive therapy over the last 2 months.
4. Uncontrolled hypo- or hyperthyroidism
5. Current tobacco use
6. Active malignancy
7. History of clinically significant cardiac, hepatic, or renal disease.
8. History of any serious hypersensitivity reaction to study medications, any other incretin mimetic, any other formulation of supplemental vitamin B12, and/or cobalt
9. Personal or family history of Leber hereditary optic nerve atrophy
10. Prisoners or subjects who are involuntarily incarcerated
11. Compulsorily detention for treatment of either a psychiatric or physical (e.g., infectious disease) illness
12. Prior history of pancreatitis, medullary thyroid cancer, or multiple endocrine neoplasia type 2 (MEN 2)
13. Serum vitamin B12 level above the upper limit of assay detection
Endpoints (50)
What's being measured
Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.
Coverage by outcome category
Weight & body composition
5 endpointsUncoupling Protein 1 (UCP1) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue)
Time frame:6 weeks after start of each intervention
change from baseline, descriptive
Posted result
| Group | Value (mean), natural log(arbitrary units) | 95% CI |
|---|---|---|
| Cyanocobalamin | 1.69 | -1.26 – 4.63 |
| Dulaglutide | 3.78 | 1.68 – 5.87 |
Uncoupling Protein 1 (UCP1) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue)
Time frame:6 weeks after start of each intervention
change from baseline, descriptive
Fat Browning Measured as Standard Uptake Value (From Positron Emission Tomography - Computed Tomography (PET-CT) Reading)
Time frame:6 weeks after start of each intervention
descriptive
Posted result
| Group | Value (mean), standard uptake value | 95% CI |
|---|---|---|
| CyanocobalaminRight side PET- CT | 0.88 | 0.23 – 1.52 |
| Left side PET-CT | 0.81 | 0.23 – 1.39 |
| DulaglutideRight side PET- CT | 1.37 | 0.48 – 2.27 |
| Left side PET-CT | 1.26 | 0.45 – 2.08 |
Nicotinamide Adenine Dinucleotide Dehydrogenase (Ubiquinone) Iron-sulfur protein3 (NDUFS3) (From Adipose Tissue)
Time frame:6 weeks after start of each intervention
change from baseline, improvement
Fat Browning Measured as Standard Uptake Value (From Positron Emission Tomography - Computed Tomography (PET-CT) Reading)
Time frame:6 weeks after start of each intervention
descriptive
Glycemic / diabetes
6 endpointsInsulin Level (From Plasma)
Time frame:6 weeks after start of each intervention
change from baseline, improvement
Posted result
| Group | Value (mean), natural log(picomoles per liter) | 95% CI |
|---|---|---|
| Cyanocobalamin | 4.10 | 3.77 – 4.43 |
| Dulaglutide | 3.86 | 3.55 – 4.16 |
Glucose Level (From Plasma)
Time frame:6 weeks after start of each intervention
Fasting glucose, change
change from baseline, improvement
LOINC 1558-6
Posted result
| Group | Value (mean), milligrams per deciliter | 95% CI |
|---|---|---|
| Cyanocobalamin | 80.61 | 76.08 – 85.14 |
| Dulaglutide | 78.50 | 74.22 – 82.78 |
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
Time frame:6 weeks after start of each intervention
HOMA-IR (insulin sensitivity)
change from baseline, improvement
Posted result
| Group | Value (mean), HOMA-IR score | 95% CI |
|---|---|---|
| Cyanocobalamin | 2.36 | 1.77 – 2.95 |
| Dulaglutide | 1.63 | 1.08 – 2.17 |
Insulin Level (From Plasma)
Time frame:6 weeks after start of each intervention
change from baseline, improvement
Glucose Level (From Plasma)
Time frame:6 weeks after start of each intervention
descriptive, improvement
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
Time frame:6 weeks after start of each intervention
HOMA-IR (insulin sensitivity)
change from baseline, improvement
Cardiometabolic biomarkers
5 endpointsFree Fatty Acids Level (From Plasma)
Time frame:6 weeks after start of each intervention
Free fatty acids, change
change from baseline, improvement
Posted result
| Group | Value (mean), natural log(nanomoles per liter) | 95% CI |
|---|---|---|
| Cyanocobalamin | -5.15 | -5.76 – -4.55 |
| Dulaglutide | -5.68 | -6.22 – -5.14 |
IL-6 (From Peripheral Blood Mononuclear Cells)
Time frame:6 weeks after start of each intervention
change from baseline, improvement
Free Fatty Acids Level (From Plasma)
Time frame:6 weeks after start of each intervention
Free fatty acids, change
change from baseline, improvement
Interleukin-4 (From Plasma)
Time frame:6 weeks after start of each intervention
concentration, descriptive
Interleukin-11 (From Plasma)
Time frame:6 weeks after start of each intervention
concentration, descriptive
Other (unclassified)
34 endpointsCytokine Interleukin-6 (IL-6) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue)
Time frame:6 weeks after start of each intervention
change from baseline, descriptive
Posted result
| Group | Value (mean), natural log(arbitrary units) | 95% CI |
|---|---|---|
| Cyanocobalamin | 7.88 | 7.16 – 8.60 |
| Dulaglutide | 7.67 | 6.98 – 8.35 |
Signal Transducer and Activator of Transcription 3 (STAT3) Band Intensity/Western Blot (From Adipose Tissue)
Time frame:6 weeks after start of each intervention
descriptive
Cytokine Interleukin-6 (IL-6) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue)
Time frame:6 weeks after start of each intervention
change from baseline, improvement
Signal Transducer and Activator of Transcription 3 (STAT3) Band Intensity/Western Blot (From Adipose Tissue)
Time frame:6 weeks after start of each intervention
descriptive
PR Domain Containing 16 (PRDM16) Messenger Ribonucleic Acid (mRNA) Level ((From Adipose Tissue)
Time frame:6 weeks after start of each intervention
descriptive
Posted result
| Group | Value (mean), natural log(arbitrary units) | 95% CI |
|---|---|---|
| Cyanocobalamin | 2.58 | 1.47 – 3.69 |
| Dulaglutide | 2.53 | 1.48 – 3.58 |
Nicotinamide Adenine Dinucleotide Dehydrogenase (Ubiquinone) Iron-sulfur protein3 (NDUFS3) (From Adipose Tissue)
Time frame:6 weeks after start of each intervention
descriptive
Beta1-adrenoceptor (ADRB1) (From Adipose Tissue)
Time frame:6 weeks after start of each intervention
descriptive
Beta2-adrenoceptor (ADRB2) (From Adipose Tissue)
Time frame:6 weeks after start of each intervention
descriptive
Beta3-adrenoceptor (ADRB3) (From Adipose Tissue)
Time frame:6 weeks after start of each intervention
descriptive
Nuclear Factor Kappa B (NfKappaB) p65 Band Intensity/Western Blot (From Peripheral Blood Mononuclear Cells)
Time frame:6 weeks after start of each intervention
descriptive
Interleukin-6 (IL-6) mRNA (From Peripheral Blood Mononuclear Cells)
Time frame:6 weeks after start of each intervention
descriptive
IL-6 (From Peripheral Blood Mononuclear Cells)
Time frame:6 weeks after start of each intervention
descriptive
Suppressor of Cytokine Signaling 3 (SOCS3) Band Intensity/Western Blot (From Peripheral Blood Mononuclear Cells)
Time frame:6 weeks after start of each intervention
descriptive
Cytokine IL-6 Level (From Plasma)
Time frame:6 weeks after start of each intervention
descriptive
Posted result
| Group | Value (mean), natural log(picograms per milliliter) | 95% CI |
|---|---|---|
| Cyanocobalamin | -0.20 | -0.93 – 0.53 |
| Dulaglutide | -0.46 | -1.15 – 0.22 |
Tumor Necrosis Factor - Alpha (From Plasma)
Time frame:6 weeks after start of each intervention
concentration, descriptive
Posted result
| Group | Value (mean), natural log(picograms per milliliter) | 95% CI |
|---|---|---|
| Cyanocobalamin | .11 | -1.22 – 1.45 |
| Dulaglutide | 0.33 | -0.28 – 0.95 |
Interleukin-4 (From Plasma)
Time frame:6 weeks after start of each intervention
concentration, descriptive
Interleukin-10 (From Plasma)
Time frame:6 weeks after start of each intervention
concentration, descriptive
Interleukin-11 (From Plasma)
Time frame:6 weeks after start of each intervention
concentration, descriptive
Interleukin-13 (From Plasma)
Time frame:6 weeks after start of each intervention
concentration, descriptive
Glucagon-like Peptide-1 (From Plasma)
Time frame:6 weeks after start of each intervention
concentration, descriptive
Posted result
| Group | Value (mean), picomoles per milliliter | 95% CI |
|---|---|---|
| Cyanocobalamin | 40.66 | 20.82 – 60.49 |
| Dulaglutide | 206.15 | 187.42 – 224.88 |
Oroboros Oxygen Consumption
Time frame:6 weeks after start of each intervention
descriptive
PR Domain Containing 16 (PRDM16) Messenger Ribonucleic Acid (mRNA) Level ((From Adipose Tissue)
Time frame:6 weeks after start of each intervention
change from baseline, descriptive
Beta1-adrenoceptor (ADRB1) (From Adipose Tissue)
Time frame:6 weeks after start of each intervention
descriptive
Beta2-adrenoceptor (ADRB2) (From Adipose Tissue)
Time frame:6 weeks after start of each intervention
descriptive
Beta3-adrenoceptor (ADRB3) (From Adipose Tissue)
Time frame:6 weeks after start of each intervention
descriptive
Nuclear Factor Kappa B (NfKappaB) p65 Band Intensity/Western Blot (From Peripheral Blood Mononuclear Cells)
Time frame:6 weeks after start of each intervention
descriptive
Interleukin-6 (IL-6) mRNA (From Peripheral Blood Mononuclear Cells)
Time frame:6 weeks after start of each intervention
change from baseline, improvement
Suppressor of Cytokine Signaling 3 (SOCS3) Band Intensity/Western Blot (From Peripheral Blood Mononuclear Cells)
Time frame:6 weeks after start of each intervention
descriptive
Cytokine IL-6 Level (From Plasma)
Time frame:6 weeks after start of each intervention
change from baseline, improvement
Tumor Necrosis Factor - Alpha (From Plasma)
Time frame:6 weeks after start of each intervention
descriptive
Interleukin-10 (From Plasma)
Time frame:6 weeks after start of each intervention
concentration, descriptive
Interleukin-13 (From Plasma)
Time frame:6 weeks after start of each intervention
concentration, descriptive
Glucagon-like Peptide-1 (From Plasma)
Time frame:6 weeks after start of each intervention
concentration, descriptive
Oroboros Oxygen Consumption
Time frame:6 weeks after start of each intervention
change from baseline, descriptive
Provenance
Sources
Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.