Your DNA stays the same.
Which genes your immune cells use changes.
The Inflammation Compass measures RNA transcript abundance and reports no DNA variants. Three ideas explain what that means.
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DNA, the fixed instructions
Your DNA is the set of genes you were born with. Its sequence stays essentially the same through life, before and during GLP-1 therapy alike, so a DNA test reads the instructions themselves.
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RNA, the working copies
When a cell uses a gene, it makes working copies of it, called messenger RNA (mRNA). Which copies a cell makes changes with what is happening around it, so mRNA in immune cells shifts with infection, exercise, sleep, illness and medication.
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Transcriptomics, counting the copies
Transcriptomics counts those copies across tens of thousands of genes in one sample. In whole blood it reads circulating immune cells, so it shows which instructions they were carrying out when the sample was taken. Routine labs such as hs-CRP measure a protein further downstream.
Six readings from 38 pathways,
with no overall score.
Gene expression is summarized into 38 pathways, 21 for Activation and 17 for Resolution. Each reading is a principal component of the pathway scores within one phase, calculated with fixed weights. Five are levels; one is a balance. The readings are statistical summaries, not six separate body functions, and a pathway can contribute to more than one.
Activation starts a response
21 pathways: danger sensing, alarm cytokines, interferon signaling, recruitment and deployment of immune cells, clotting and complement.
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Activation Level
The fast, built-in alarm. These signals raise fever, call in immune cells, and get a response started.
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Targeted Defense
The targeted part of the response. These signals show a threat to T cells and power up the cells that kill marked targets.
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Where the Fast Response Is Working
Where the fast response is happening: mainly in the blood, or moving cells out into tissue. A balance between two sets of pathways, not a level.
Resolution ends it
17 pathways: feedback and calming signals, regulatory T cells and repair signals, and the clearance of spent cells.
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Resolution Level
Early feedback and calming signals that keep a response from running on.
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Regulatory Cells & Repair Signals
Regulatory T cells and repair signals that hold a response down over time.
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Clean-up & Rebuilding
Spent immune cells are cleared away and the body shifts toward repair.
The immune cell mix
Reference-based deconvolution estimates, from the same RNA data, the share of T cells, B cells, killer cells, dendritic cells, monocytes, and neutrophils and related cells. It helps separate a change in how many of a cell type are present from a change in what those cells are doing. It is an estimate and doesn’t replace a blood count.
Why both halves matter for GLP-1 research
Published GLP-1 studies have mostly measured Activation-side markers such as hs-CRP, TNF-α and IL-1β.1,2 Routine labs don’t report the signals that end a response directly. Reading both halves from one sample shows which parts of the inflammation system moved across samples, on either side.
Different measurements
change on different timescales.
In trials of GLP-1 medicines, each kind of measurement moved at its own pace. These are trial averages; they describe the medicines, not where any one person’s results sit.
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Hours to weeks: immune-cell gene activity
In a 24-person exenatide trial, reactive oxygen species generation by circulating mononuclear cells fell within hours of a single dose, and inflammatory gene expression in those cells was lower after 12 weeks.2
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Weeks: hs-CRP
In SELECT, hs-CRP was about 12% lower by week 4 and 19% lower by week 8 in the European subpopulation, when participants had lost about 1.4% and 2.8% of body weight.1
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Weeks to months: lipids, liver enzymes and A1C
Fasting glucose moves within weeks, while A1C reflects the previous 2–3 months.
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Months: weight
Average weight loss in the STEP and SURMOUNT trials continued for more than a year before leveling off.
In trials, inflammation markers fell
before most of the weight was lost.
On GLP-1 receptor agonists, hs-CRP falls within weeks, before most weight is lost, and falls even in some people who lose little weight. Larger falls track with greater weight loss, so weight-dependent and weight-independent routes both appear to contribute.
SELECT: early and partly weight-independent
In a prespecified secondary analysis of SELECT, semaglutide 2.4 mg in people with established cardiovascular disease and overweight or obesity lowered hs-CRP by 37.8% at week 104. hs-CRP was already about 12% lower at week 4 and 19% lower at week 8 in the European subpopulation, before full dose escalation. It fell even in participants who did not lose weight, though larger falls tracked with greater weight loss, and modeling suggests lower inflammation accounts for part of the cardiovascular benefit.1
Chaudhuri: gene expression in circulating mononuclear cells
In a randomized trial of exenatide in type 2 diabetes, mRNA for TLR2, TLR4, TNF-α and IL-1β in circulating mononuclear cells, and NF-κB binding activity, fell by 16–31% over 12 weeks without weight loss. The trial is small, and it measured a single GLP-1 receptor agonist.2
Across the class, and tirzepatide
Three meta-analyses in type 2 diabetes, each pooling 40–52 randomized trials, found class-wide reductions in CRP (standardized mean difference −0.59 to −0.63 in the two that report it).9,13,14 For tirzepatide, a meta-analysis found hs-CRP about 33% lower than placebo, and a phase 2 analysis found ICAM-1 and YKL-40 reductions within 4 weeks at higher doses.8,12 In SURMOUNT-OSA, improvements in sleep apnea measures mediated part of the hs-CRP reduction beyond weight loss.7
GLP-1 anti-inflammatory evidence, summarized
Randomized trials, a mechanistic trial in circulating mononuclear cells, and meta-analyses.
| Study | Design and participants | Inflammation finding | Evidence type |
|---|---|---|---|
| SELECT hs-CRP 1 Plutzky et al., Circulation 2026 | Semaglutide 2.4 mg vs placebo, n = 17,604 with established CVD, up to 208 weeks | hs-CRP −37.8% at week 104; −12% at week 4 and −19% at week 8; fell even with minimal weight loss | Prespecified secondary analysis of an RCT |
| Chaudhuri 2012 2 J Clin Endocrinol Metab 2012 | Exenatide 10 mcg twice daily vs placebo, n = 24, type 2 diabetes, 12 weeks | Mononuclear-cell TLR2, TLR4, TNF-α and IL-1β mRNA and NF-κB binding 16–31% lower, without weight loss | Small mechanistic RCT |
| STEP 1, 2, 3 5 Verma et al., EClinicalMedicine 2023 | Semaglutide 2.4 mg vs placebo, 68 weeks, overweight or obesity with and without T2D | hs-CRP −44%, −39%, −48% vs placebo; reductions correlated with weight, waist and HOMA-IR | Exploratory analyses of three phase 3 RCTs |
| STEP-HFpEF 6 Kosiborod et al., N Engl J Med 2023 | Semaglutide vs placebo, n = 529, HFpEF with obesity, 52 weeks | CRP −43.5% vs −7.3% for placebo, alongside improvements in symptoms and function | Phase 3 RCT |
| SURMOUNT-OSA 7 Malhotra et al., Nat Med 2026 | Tirzepatide vs placebo, moderate-to-severe OSA with obesity, 52 weeks | Sleep apnea improvements mediated part of the hs-CRP reduction, beyond weight loss | Mediation analysis of an RCT |
| Type 2 diabetes meta-analyses 9,13,14 Bray 2021, Ren 2025, Alrasheed 2026 | 40–52 RCTs each, n ≈ 4,700–6,700, type 2 diabetes, several GLP-1 receptor agonists | CRP SMD −0.59 to −0.63 (Ren, Alrasheed; Bray reported −0.54 mg/L); TNF-α SMD −0.39 to −0.92; adiponectin higher (Bray, Ren) | Meta-analyses of RCTs |
White blood cells carry little GLP-1 receptor,
so the routes to them are indirect.
GLP-1 receptor transcript was undetectable in circulating mononuclear cells in a liraglutide trial substudy.11 Wong and Drucker review the routes by which GLP-1 medicines could still change gene activity in blood cells.3
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Brain to immune system
GLP-1 medicines reach GLP-1 receptors in the brain. In mice, activating central GLP-1 receptors suppressed TLR-induced inflammation throughout the body through α-adrenergic and opioid receptor signaling.4
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Fat tissue
Fat tissue in obesity releases inflammatory signals such as TNF-α, IL-6 and MCP-1. As it shrinks, less of that signal reaches the blood, which would reduce the priming of circulating monocytes and neutrophils. This route depends on weight loss, so it can’t explain the early, weight-independent changes.3
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Gut barrier
Preclinical studies suggest GLP-1 signaling in the gut strengthens the intestinal barrier and limits the passage of bacterial lipopolysaccharide into the blood, which would mean less TLR2 and TLR4 stimulation of circulating monocytes. Evidence in people is limited.3
So the Inflammation Compass doesn’t measure the drug acting on blood cells. It measures gene activity in circulating immune cells while you’re on therapy, and across samples it shows which parts of the inflammation system moved and by how much.
From one tube of blood
to six readings you can trace.
The Inflammation Compass is a laboratory-developed test based on stranded whole-transcriptome RNA sequencing of stabilized venous blood, run in a CLIA-certified laboratory.
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Collection and RNA stabilization
Venous blood is drawn into a PAXgene tube containing an RNA stabilizer, which holds the transcription profile at the moment of collection and limits gene induction and RNA breakdown in transit.10
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Sequencing
After RNA extraction, quality checks and DNA removal, globin mRNA and ribosomal RNA are depleted. Stranded libraries with ERCC spike-in controls are sequenced on Illumina NovaSeq instruments at about 30 million read pairs per sample (2×150 bp). A sample that fails quality thresholds is re-processed or re-collected and never reported.
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Pathway scoring
Reads are aligned (STAR) and counted per gene (featureCounts). Genes are scored as 38 curated pathways, drawn from peer-reviewed research and pathway databases and checked against a reference collection of human blood transcriptomes. Each pathway is scored relative to overall gene activity in the same sample, so results are robust to differences in sequencing depth between runs.
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Readings and comparison
A statistical model with fixed weights combines the 38 pathways into six readings, and the immune cell mix is estimated from the same data. Each result is placed against a reference group, people whose blood was measured the same way, and, from the second sample, against your own earlier samples. Method versions are recorded so each sample’s calculation can be traced.
Biomeme has built DNA and RNA tests, and the instruments that run them, for almost 15 years, first for field biologists, the military and diagnostic labs. Biomeme Labs is its clinical laboratory. Read more on Biomeme’s website.
What it
can't tell you.
The measurement is RNA in whole blood at a single time point. Reading names are an inference about what those signals are associated with, and blood shows some parts of the inflammation system only partly. Results vary with time of day, recent activity, illness, sleep, stress and hydration.
The report shows what changed and by how much, not why. It doesn’t show whether a medication is working or safe, measure drug levels or muscle, or diagnose, rule out or predict any disease. That the six readings respond to GLP-1 therapy is biologically expected but not yet demonstrated. The reference group is still growing, and a study of how much results vary within one person is planned.
The Inflammation Compass is a laboratory-developed test with a general wellness intended use, run in a CLIA-certified laboratory. It is not FDA cleared or approved. What a change means is for you and your clinician to weigh.
Frequently asked questions
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What is GLP-1 transcriptomic monitoring?
It means reading messenger RNA in circulating immune cells in samples taken during GLP-1 therapy. Your DNA sequence stays essentially fixed, while mRNA shows which genes your immune cells were using when the sample was taken. The Inflammation Compass summarizes that into six readings from 38 pathways, plus your immune cell mix, and from your second sample shows which readings moved and by how much. It doesn’t show whether the medication is working.
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How is transcriptomic monitoring different from a standard blood test?
Standard tests measure proteins, metabolites and cell counts in the blood. hs-CRP, for example, measures one protein released by the liver, and it can’t show which part of the inflammation system is involved. Whole-blood RNA sequencing reads gene activity in immune cells across Activation and Resolution pathways, including the signals that end a response, which routine tests don’t report directly. It adds to standard tests and doesn’t replace them.
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Can transcriptomic monitoring detect muscle loss from GLP-1 therapy?
No. Whole-blood RNA sequencing reads circulating white blood cells, not skeletal muscle, and can’t measure muscle-specific markers such as MuRF1 or MAFbx. Lean mass is measured with body-composition scans such as DXA. The Inflammation Compass measures something different, and its results sit alongside your scans rather than standing in for them.
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How quickly can immune-cell gene activity change on GLP-1 therapy?
In a small exenatide trial, inflammatory gene expression in circulating mononuclear cells was lower after 12 weeks, and in SELECT hs-CRP was lower by week 4. Weight and A1C settle over months. A sample before you start and another after a few weeks or a dose change shows which readings moved and by how much. The report marks a reading as moved only when the shift is larger than the usual difference between two samples taken close together, and a change shows direction, not cause.
Read more
- What RNA adds
The shorter version of this page, written for everyday reading.
- How the Inflammation Compass works
The full method, validation status and limits for the test itself.
- GLP-1 biomarkers
What hs-CRP, blood counts and other routine markers measure, and what the six readings add.
- When to give a sample
A suggested cadence from baseline through maintenance. You choose how often.
See which parts of your inflammation move while you're on therapy.
Each sample shows where your six readings sit, compared with people measured the same way, and what moved since the last one.
Sources and further reading
References
Clinical trials, mechanistic studies, reviews and methods sources cited on this page.