Josefa García Barrado
Full Professor of Pharmacology and researcher in the Neuroendocrinology and Obesity group at the University of Salamanca
The study appears to be well-conducted and, from a methodological standpoint, can be considered of high quality. It addresses a clinically relevant question and provides interesting evidence regarding the potential genetic contribution to variability in response to GLP-1 receptor agonists, both in terms of weight loss and adverse effects. Furthermore, it aligns reasonably well with existing evidence, which suggests that the response to this type of treatment is heterogeneous and likely multifactorial. In that sense, the study is valuable because it contributes to a better understanding of that variability and opens up a promising line of research in the field of personalized medicine.
However, I believe the practical implications of the findings are somewhat overemphasized in the final interpretation. Although genetic associations are identified, the effect sizes are modest and few, and from a clinical standpoint, their immediate utility appears limited. Non-genetic factors such as age, sex, baseline metabolic status, adherence, or tolerance to treatment likely carry greater weight and, furthermore, are more accessible and applicable variables in routine clinical decision-making. Therefore, although the study is interesting from a biological standpoint and may be useful for generating hypotheses or for future, more comprehensive predictive models, the results alone do not yet justify direct clinical application or the routine use of genetic testing to guide treatment.