Weight loss from glucagon-like peptide-1 receptor agonists by genetic factors in adults with type 2 diabetes
Authors' conclusion
BMI PRS could potentially be used to personalize obesity management with GLP-1RAs. Large-scale, multi-ancestry studies are needed to validate the application.
Study context
- Population
- Adults with T2D treated with GLP-1 RA; mean age 59 ± 11 years, 55 % female
- Participants
- 1,055 adults
- Comparison
- Intermediate and high vs low BMI polygenic risk score
- Outcome
- Weight loss percentage
- Follow-up
- 52 weeks
Methodological detailslinear mixed models, genotype × follow-up time interaction, BMI polygenic risk score (PRS) incorporated 935,416 single-nucleotide polymorphisms (SNPs)
- Linear mixed models
- Genotype × follow-up time interaction
- BMI PRS incorporated 935,416 SNPs
Main finding
As reported in the abstract
Difference
0.7 %
P = 0.0017
Intermediate BMI PRS · less weight loss with Intermediate BMI PRS
Difference
1.5 %
P = 0.0023
High BMI PRS · less weight loss with High BMI PRS
Further findings
Five major genetic variants for BMI PRS (individual SNPs)
- Individual SNPs showed no significant association with weight loss
- Several genotypes showed significant time-varying effects
BMI PRS × time interaction
- Intermediate PRS showed less early weight loss
- High PRS showed less late weight loss
Original publication
Weight loss from glucagon-like peptide-1 receptor agonists by genetic factors in adults with type 2 diabetes. Diabetes Res Clin Pract. Published 3 December 2025. doi:10.
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