Phase 4
N=23
GLP-1 Therapy: The Role of IL-6 Signaling and Adipose Tissue Remodeling in Metabolic Response
Glucose Intolerance · Overweight and Obesity · Drug Effect · Adiposity
Bottom Line
View on ClinicalTrials.gov: NCT04387201 ↗Enrolled (actual)
23
Serious AEs
0.0%
Results posted
Dec 2024
Primary outcome: Primary: Cytokine Interleukin-6 (IL-6) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue) — 7.88; 7.67 natural log(arbitrary units)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Cyanocobalamin (Drug); Dulaglutide (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- The University of Texas Health Science Center, Houston
- Primary completion
- Oct 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cytokine Interleukin-6 (IL-6) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue) |
7.88; 7.67 | — |
| PRIMARY Uncoupling Protein 1 (UCP1) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue) |
1.69; 3.78 | — |
| PRIMARY Signal Transducer and Activator of Transcription 3 (STAT3) Band Intensity/Western Blot (From Adipose Tissue) |
— | — |
| SECONDARY PR Domain Containing 16 (PRDM16) Messenger Ribonucleic Acid (mRNA) Level ((From Adipose Tissue) |
2.58; 2.53 | — |
| SECONDARY Nicotinamide Adenine Dinucleotide Dehydrogenase (Ubiquinone) Iron-sulfur protein3 (NDUFS3) (From Adipose Tissue) |
— | — |
| SECONDARY Beta1-adrenoceptor (ADRB1) (From Adipose Tissue) |
— | — |
| SECONDARY Beta2-adrenoceptor (ADRB2) (From Adipose Tissue) |
— | — |
| SECONDARY Beta3-adrenoceptor (ADRB3) (From Adipose Tissue) |
— | — |
| SECONDARY Nuclear Factor Kappa B (NfKappaB) p65 Band Intensity/Western Blot (From Peripheral Blood Mononuclear Cells) |
— | — |
| SECONDARY Interleukin-6 (IL-6) mRNA (From Peripheral Blood Mononuclear Cells) |
— | — |
| SECONDARY IL-6 (From Peripheral Blood Mononuclear Cells) |
— | — |
| SECONDARY Suppressor of Cytokine Signaling 3 (SOCS3) Band Intensity/Western Blot (From Peripheral Blood Mononuclear Cells) |
— | — |
| SECONDARY Cytokine IL-6 Level (From Plasma) |
-0.20; -0.46 | — |
| SECONDARY Free Fatty Acids Level (From Plasma) |
-5.15; -5.68 | — |
| SECONDARY Insulin Level (From Plasma) |
4.10; 3.86 | — |
| SECONDARY Glucose Level (From Plasma) |
80.61; 78.50 | — |
| SECONDARY Tumor Necrosis Factor - Alpha (From Plasma) |
.11; 0.33 | — |
| SECONDARY Interleukin-4 (From Plasma) |
— | — |
| SECONDARY Interleukin-10 (From Plasma) |
— | — |
| SECONDARY Interleukin-11 (From Plasma) |
— | — |
| SECONDARY Interleukin-13 (From Plasma) |
— | — |
| SECONDARY Glucagon-like Peptide-1 (From Plasma) |
40.66; 206.15 | — |
| SECONDARY Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) |
2.36; 1.63 | — |
| SECONDARY Fat Browning Measured as Standard Uptake Value (From Positron Emission Tomography - Computed Tomography (PET-CT) Reading) |
0.88; 1.37; 0.81; 1.26 | — |
| SECONDARY Oroboros Oxygen Consumption |
— | — |
Summary
This project investigates the anti-obesity mechanisms of glucagon-like peptide-1 (GLP-1) analogs, which are used in the treatment of human obesity and diabetes mellitus. The investigators will test if GLP-1 induces secretion of interleukin-6 (IL-6), a cytokine that may collaborate with GLP-1 analogs to induce the formation of brown fat, which has anti-diabetic properties. The results will guide future obesity and diabetes mellitus therapies.
Eligibility Criteria
Inclusion criteria
- Men and women, ages 18-50 years
- 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%.
- BMI ≤ 35 kg/m2
- 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
- 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
- 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.
- 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.
- If patient takes thyroid medications, these must be dosed to control hypo- or hyperthyroidism.
Exclusion Criteria
- History of Type 1 or Type 2 diabetes mellitus
- Pregnant or breastfeeding women
- Medications: Beta blockers, corticosteroids, monoamine oxidase inhibitors, diabetes medications (including incretin mimetics and thiazolidinediones), and/or immunosuppressive therapy over the last 2 months.
- Uncontrolled hypo- or hyperthyroidism
- Current tobacco use
- Active malignancy
- History of clinically significant cardiac, hepatic, or renal disease.
- History of any serious hypersensitivity reaction to study medications, any other incretin mimetic, any other formulation of supplemental vitamin B12, and/or cobalt
- Personal or family history of Leber hereditary optic nerve atrophy
- Prisoners or subjects who are involuntarily incarcerated
- Compulsorily detention for treatment of either a psychiatric or physical (e.g., infectious disease) illness
- Prior history of pancreatitis, medullary thyroid cancer, or multiple endocrine neoplasia type 2 (MEN 2)
- Serum vitamin B12 level above the upper limit of assay detection
Data sourced from ClinicalTrials.gov (NCT04387201). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.