Genetic Variations Influence Weight Loss and Side Effects of Obesity Drugs
A recent study, analysing data from 15,000 individuals, indicates that genetic predispositions play a role in how much weight people lose when using popular obesity drugs and their susceptibility to adverse reactions, such as nausea and vomiting.
Genetic Links to Efficacy and Side Effects
The medications, which mimic a natural gut hormone to induce feelings of fullness, show varied results among users. While some achieve substantial weight loss, others experience minimal change or severe side-effects. The research pinpointed a genetic variant associated with increased weight loss, averaging an additional 0.76kg, and a higher incidence of nausea. Individuals carrying two copies of this variant, more prevalent in those of European ancestry, could double this additional weight loss.
Furthermore, another genetic variant was identified as potentially increasing the severity of vomiting for some users of tirzepatide (Mounjaro), making it up to 15 times worse than normal for a small percentage of patients.
Broader Context and Future Implications
While the genetic influence is described as modest by Professor Ruth Loos of the University of Copenhagen, it is deemed comparable to other influential factors. However, experts like Dr Marie Spreckley from the University of Cambridge emphasise that genetics are just one component within a complex interplay of behavioural, clinical, and treatment-related elements, including diet, exercise, and support.
Other factors, such as sex, age, and ethnicity, have also been observed to affect treatment outcomes. For instance, women are reportedly more likely to achieve significant weight loss than men on Mounjaro, and younger, white or Asian individuals may experience greater weight reduction.
Professor Naveed Sattar from the University of Glasgow, a metabolic health expert, notes that while these findings are scientifically intriguing, they are still a considerable way from transforming clinical practice. The ultimate goal is to move towards 'precision medicine', where genetic and other personal data could guide the selection of the most suitable weight-loss drug, but more robust trial data is required to define the balance of benefits and harms effectively.
