Why don't some people lose weight on Wegovy?

Clinical trials have shown that people using weight-loss injections such as Wegovy and Mounjaro lose between 16% and 21% of their body weight. However, these drugs do not work for everyone.

In the trials, the group of participants lost less than 5% of their body weight (a weight loss of 5% or more is considered “clinically significant”). So-called “non-responders” accounted for 10% to 15% of the participants. Outside the tightly controlled conditions of clinical trials, up to 20% of people respond poorly to these drugs, according to obesity experts told The Associated Press. Why might that be?

First, it’s important to understand that the causes of obesity are multifactorial. Our understanding of the genetic basis of obesity has expanded significantly over the past decade, and it’s become clear that for many people, genetic variations have a significant impact on their weight. For example, a 2021 study found that 0.3% of the UK population (equivalent to more than 200,000 people) have a genetic mutation in part of the brain circuit that regulates appetite, leading to an average weight gain of 17 kg by age 18.

This genetic variation in the underlying causes of obesity may be one explanation why some people show poor response to these drugs.

It's also important to understand how these new anti-obesity drugs work. Anyone who has tried to lose weight through diet and exercise knows that such attempts are usually accompanied by increased hunger and fatigue.

This is the body's normal response to weight loss. It is designed to protect what the brain considers its "normal" weight, which for some people may be in the obese range. New weight-loss drugs work by turning off this physiological response, making it easier to lose weight through changes in diet and activity levels.

During the clinical trials, participants were provided with physical activity support, access to dietitians and psychologists. These specialists provided participants with individualized help with lifestyle changes to maximize the effectiveness of these drugs.

This support is rarely available to people outside of clinical trials, and its absence can limit the effectiveness of drugs if the necessary lifestyle changes are not supported by experts.

Several studies have attempted to identify factors that may predict response to weight loss medications. One common factor for clinically significant weight loss is higher baseline body weight.

Strong excitement

Since the introduction of these drugs, media reports have generated huge demand among both those for whom they are intended (obese people) and those who are not obese but want to lose a few pounds.

In the UK, the National Institute for Health and Care Excellence (NICE) sets guidelines on the clinical parameters needed to prescribe the drug. For Wegovy and Mounjaro, a person must have obesity and at least one related health problem, such as sleep apnoea or high blood pressure.

Due to the lack of alternative effective weight loss drugs, and perhaps also due to media coverage, there have been reports of these drugs being prescribed to people who do not meet NICE criteria.

One possible consequence of this is that people who are lower than the guidelines weight are given these weight-loss drugs and, as a result, lose less weight than clinical trials show.

Despite the minority of people for whom these drugs do not work, their introduction promises to provide significant health benefits to millions of people who have previously tried unsuccessfully to lose weight.