Dolores Corella
CIBEROBN researcher and professor of preventive medicine at the University of Valencia
Is this a high-quality study?
"This study is very interesting and provides relevant data. However, its design has some limitations, as it is not a pre-designed and registered clinical trial; rather, it uses data from participants who had previously taken part in genetic studies conducted by a genetic testing company for a different purpose. The study now analyzes individuals taking weight-loss medications and their weight loss, linking these outcomes to their genetic characteristics. What is novel is that they find a strong association between a genetic variant in the GLP-1R gene and greater weight loss when taking the drug. This finding is important. They also find some associations between genetic variants in the GLP-1R and GIPR genes and some of the adverse effects of weight-loss drugs."
Are there any limitations to consider?
“The limitation is that it needs to be replicated in other studies before being incorporated into clinical practice, as it does not have the design of a randomized, controlled clinical trial specifically designed for this purpose.”
What are the implications, and how does this fit with existing evidence?
“The implications are significant because it contributes new evidence on how genetic variants can determine the effects of the same drug, making them more effective in some people than others, and whether or not they may be associated with adverse effects. It fits very well within the existing evidence, and these results will be applicable in the new era of precision medicine.”
Genetic effects are modest compared to non-genetic factors. What does this imply for clinical practice?
“In this case, the genetic effect is not very small in magnitude. It is just one genetic variant in the context of significant weight loss. It amounts to nearly a kilo difference in weight lost with the same treatment and duration. If other genetic variants are found, the effect may be cumulative, and the important thing is that it provides new relevant data in pharmacogenetics and the genetic epidemiology of obesity. Likewise, the association of certain genetic variants with greater or lesser adverse effects, such as vomiting, etc., is relevant for better personalizing treatments, including with new weight-loss drugs.”