Ana Belén Crujeiras Martínez
Director of the Epigenomics Research Group within the Endocrinology and Nutrition Group at the Santiago Health Research Institute (IDIS) and a member of the CIBER Network on the Pathophysiology of Obesity and Nutrition (CIBERobn)
Is the study of high quality?
“Yes, it’s a solid piece of work. It analyzes nearly 28,000 people and uses advanced genetic tools (GWAS), in addition to validating some of the results with real clinical data. Methodologically speaking, it’s a robust and well-executed study.”
Are there any limitations to consider?
“Much of the data is self-reported, which can introduce bias. Additionally, the sample is predominantly drawn from the U.S. population of European descent, so the results cannot be automatically extrapolated to other countries like Spain. And, above all, the genetic effects detected are small.”
What are the implications, and how does this fit with existing evidence?
“It aligns well with expectations: it confirms that there is a biological and pharmacogenetic basis for the response to GLP-1, but also that clinical variability is multifactorial. It reinforces the path toward precision medicine, although still in its early stages, and is consistent with previous evidence of great heterogeneity in response to these drugs.”
Genetic effects are modest compared to non-genetic factors. What does this imply for clinical practice?
“It implies that, at present, it is much more useful and efficient to adjust treatment based on modifiable clinical variables (dose, adherence, comorbidities, age, sex) than to rely on genetic testing. Genetics may provide complementary information in the future, but its current clinical utility is limited. Furthermore, from a modern perspective on obesity, environmental factors—which also act via epigenetic mechanisms—remain the primary determinants and, therefore, the main therapeutic target.
In summary: the study provides highly relevant evidence as a starting point toward personalized medicine in obesity. However, at this time the priority should not be to generalize the use of genetic testing, but rather to develop more comprehensive approaches that integrate clinical data, environmental factors, and, likely, epigenetic markers, since the latter better reflect the interaction between the environment and each patient’s biology.”