Genetic Resistance to Weight-Loss Drugs Uncovered by New Research
Weight-loss medications such as Wegovy and Mounjaro, used by an estimated 2.4 million Britons, are not universally effective, with new scientific findings pointing to genetic influences that can hinder their results. These injections, classified as GLP-1 receptor agonists, function by imitating a natural hormone that controls blood sugar, appetite, and digestion. However, a recent study indicates that approximately one in ten individuals may experience reduced efficacy due to specific genetic variants.
The Science Behind GLP-1 Resistance
Research conducted by Stanford Medicine scientists, published in the journal Genome Medicine, identifies genetic variants present in about 10% of the population that lead to a condition termed GLP-1 resistance. This condition results in elevated levels of the GLP-1 hormone, which are less biologically effective, necessitating higher amounts to achieve the same impact on weight loss and blood sugar regulation.
The study focused on a genetic variant affecting an enzyme known as PAM (peptidyl-glycine alpha-amidating monooxygenase), which activates GLP-1 and is more prevalent in individuals with diabetes. Contrary to expectations, researchers discovered that people with this variant had higher GLP-1 levels but slower reductions in blood sugar, highlighting a complex biological response.
Dietitian Insights on Weight-Loss Variability
Ro Huntriss, a registered dietitian who works with patients on GLP-1 treatments, emphasises that weight loss outcomes exist on a spectrum. While most users lose between 10 and 20 percent of their body weight, some may only achieve a 5 percent reduction. She notes that individuals with type 2 diabetes, for instance, tend to lose less weight on average compared to those who are metabolically healthier.
"This narrative isn't necessarily communicated widely," Ms Huntriss told The Independent. "Although the science is in its infancy, this research supports the idea that, in some cases, variability in response may be influenced by biological factors beyond adherence or effort."
Multifactorial Influences on Drug Efficacy
Ms Huntriss cautions that genetic resistance is just one component of a larger puzzle. Factors such as insulin resistance, differences in dopamine and reward sensitivity, diet, lifestyle, and medication management all contribute to how effectively these drugs promote weight loss. She advises that relying solely on GLP-1 injections may be insufficient; incorporating a diet rich in protein and fibre, along with a reduced calorie intake, is crucial for optimal results.
"Our dietary habits still need to change, our calorie intake needs to be significantly lower than what it was, to lose weight," she explained. "Eating the right diet can actually drastically reduce the side effects, which then means adherence is greater, which then means the weight loss is better."
Practical Implications for Patients and Practitioners
While GLP-1 drugs are effective for the majority, Ms Huntriss acknowledges they may not be suitable for everyone. She recommends that patients and healthcare providers collaborate to assess whether the treatment is working, considering behavioural and medication management aspects. If desired outcomes are not met, alternative approaches may be necessary.
"The bottom line is between the patient and practitioner to understand: 'is this working for me', and if it’s not, and no more can be done from the behavioural and medication management point of view, then GLP-1s may not be the most appropriate medication for that person," she concluded.
The findings underscore the importance of personalised medicine in obesity treatment, as genetic testing, though not yet recommended due to early-stage science, could eventually help tailor interventions for better weight-loss success.
