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

What Was Tested

In this phase 4 trial, researchers set out to test Cyanocobalamin (Vitamin B12) and Dulaglutide.

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.

It had two arms (groups): Cyanocobalamin, then Dulaglutide (experimental) and Dulaglutide, then Cyanocobalamin (experimental).

The registry classes the interventions as drug.

More on the Plan

The investigators discovered that plasma IL-6 induction occurs through GLP-1 receptor (GLP-1R) stimulation in leukocytes.

Interestingly, studies in rodents indicate that GLP-1 / GLP-1R signaling also induces AT beiging.

Based on these observations, the investigators hypothesize that incretins induce AT browning in part via transient IL-6 / IL-6 receptor (IL-6R) / STAT3 signaling.

Studies will be paralleled in a human clinical trial, a human cell culture model, and a mouse diet-induced obesity model.

Who Took Part

Enrollment: 23 actual participants took part.

It was open to people of any sex aged from 18 years up to 50 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Men and women, ages 18-50 years. BMI ≤ 35 kg/m2. 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.

The full record lists 8 inclusion and 13 exclusion criteria; among the exclusions: pregnant or breastfeeding women; uncontrolled hypo- or hyperthyroidism; current tobacco use.

How the Study Was Run

The set-up was non-randomized, crossover and open-label.

Each person switched between Cyanocobalamin (Vitamin B12) and the comparison at some point, usually with a gap in between.

Being open-label, the Cyanocobalamin (Vitamin B12) study did not mask who received what.

It started in 2020-05-15 with completion listed for 2023-10-06.

It ran at 1 site in United States.

Its stated primary purpose is basic science.

What Was Measured

The main thing measured (primary outcome): Cytokine Interleukin-6 (IL-6) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue) (time frame: 6 weeks after start of each intervention). Uncoupling Protein 1 (UCP1) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue) (time frame: 6 weeks after start of each intervention). Signal Transducer and Activator of Transcription 3 (STAT3) Band Intensity/Western Blot (From Adipose Tissue) (time frame: 6 weeks after start of each intervention).

It also tracked 22 secondary outcomes, for example PR Domain Containing 16 (PRDM16) Messenger Ribonucleic Acid (mRNA) Level ((From Adipose Tissue), Nicotinamide Adenine Dinucleotide Dehydrogenase (Ubiquinone) Iron-sulfur protein3 (NDUFS3) (From Adipose Tissue), Beta1-adrenoceptor (ADRB1) (From Adipose Tissue), Beta2-adrenoceptor (ADRB2) (From Adipose Tissue), Beta3-adrenoceptor (ADRB3) (From Adipose Tissue) and Nuclear Factor Kappa B (NfKappaB) p65 Band Intensity/Western Blot (From Peripheral Blood Mononuclear Cells).

What This Means in Plain Language

Put simply, this is a phase 4, non-randomized trial of Cyanocobalamin (Vitamin B12) and Dulaglutide in 23 people.

Its size is small, so on its own it can only give an early look.

The trial is marked completed; results are posted on the registry, and this page does not restate them.

More context: the Cyanocobalamin (Vitamin B12) compound page and the Dulaglutide compound page, all human trials.