A multi-omics analysis of a Phase II trial identified the protein GYG1 as a dual biomarker that both predicts and tracks weight-loss response to the GLP-1 receptor agonist GZR18.
Dual biomarker: GYG1Both predicts weight-loss trajectory before treatment and tracks ongoing response during GLP-1RA therapy
What the researchers found
GYG1 (glycogenin-1) emerged as a dual-function biomarker for GLP-1 receptor agonist therapy: baseline GYG1 levels predicted the trajectory of weight loss (BMI slope), while changes in GYG1 during treatment tracked ongoing treatment response (%BMI change).
The GLP-1RA GZR18 produced dose-dependent BMI reductions, with the 48 mg biweekly dose yielding the steepest declines. Gene set enrichment analysis revealed that starch/sucrose metabolism pathways modulated ongoing drug efficacy through integrated molecular networks.
Why it matters
GLP-1 receptor agonists like semaglutide and tirzepatide have transformed obesity treatment, but not everyone responds equally well. A reliable blood-based biomarker that predicts who will benefit most — and monitors response in real time — could enable truly personalized obesity therapy, helping doctors choose the right drug and dose for each patient.
How the study worked
Longitudinal multi-omics profiling (proteomics, metabolomics, and lipidomics) was performed on 221 plasma samples from 25 participants treated with GZR18 across nine time points over 30 weeks. High-resolution mass spectrometry was used for molecular quantification. Theil-Sen regression modeled baseline predictors, while linear regression identified longitudinal biomarkers. Significant candidates were validated through gene set enrichment analysis (KEGG pathways) and STRING protein network integration.
What this study cannot tell us
The study had a very small sample size (n=25), which limits the statistical power and generalizability of the findings. Results come from a substudy of a single Phase II trial of one specific GLP-1RA (GZR18) and may not apply to other drugs in the class. External validation in larger, independent cohorts is needed before GYG1 can be used clinically.
How to read the evidence
This is a substudy of a Phase II clinical trial with multi-omics validation. While the clinical trial context strengthens the evidence, the very small sample size (n=25) means findings require independent replication.
When this study was published
Published in 2026, this is a very recent study reflecting the latest advances in precision obesity pharmacotherapy.
The bigger picture
The GLP-1 receptor agonist market is one of the fastest-growing in pharmaceutical history, yet there are no validated biomarkers to predict individual response. This study is part of a growing push toward precision obesity medicine — using molecular signatures to match patients with the therapies most likely to work for them, rather than relying on trial and error.
Questions still open
- Does GYG1 also predict response to other GLP-1 receptor agonists like semaglutide or tirzepatide?
- Can GYG1 levels be measured with a simple clinical blood test, and at what cost?
- Would a larger validation study confirm the predictive value of GYG1 across diverse patient populations?
Common questions
What is GYG1 and what does it normally do in the body?
Could this biomarker help decide which weight-loss drug to prescribe?
Read the original research
GYG1 as a Dual Biomarker of Glucagon-Like Peptide-1 Receptor Agonist Weight-Loss Response: Findings from an Integrative Multi-Omics Substudy of a Phase II Trial.
Endocrinology and metabolism (Seoul, Korea)
Citation
Li, Lijun; Hou, Mengyu; Gao, Qiannan; Dong, Ruihua. (2026). GYG1 as a Dual Biomarker of Glucagon-Like Peptide-1 Receptor Agonist Weight-Loss Response: Findings from an Integrative Multi-Omics Substudy of a Phase II Trial.. Endocrinology and metabolism (Seoul, Korea). https://doi.org/10.3803/EnM.2025.2641