Clinical trials indicate that individuals utilizing weight-loss injections, such as Wegovy and Mounjaro, can experience a reduction in body weight ranging from 16% to 21%. However, these medications do not yield results for every individual.
Within these trials, a subset of participants experienced a weight loss of less than 5%, which is deemed “clinically meaningful” only when it exceeds this threshold. These non-responders constituted approximately 10% to 15% of the trial population. According to anecdotal evidence shared by obesity specialists with the Associated Press, it is suggested that outside the controlled environment of clinical trials, up to 20% of individuals may not respond effectively to these treatments. What could account for this phenomenon?
It is crucial to acknowledge that the factors contributing to obesity are complex and varied. Over the past decade, our comprehension of the genetic factors influencing obesity has advanced considerably, indicating that genetic differences can significantly impact an individual’s weight. For instance, a study conducted in 2021 revealed that 0.3% of the UK population, which translates to over 200,000 individuals, possess a genetic mutation affecting brain circuitry that regulates appetite, resulting in an average weight gain of 17 kg by the age of 18.
This genetic diversity in the fundamental causes of obesity may help explain why certain individuals exhibit a diminished response to these medications. Additionally, it is essential to understand the mechanisms by which these new anti-obesity drugs operate. Those who have attempted weight loss through dietary changes and physical activity are often met with heightened sensations of hunger and fatigue.
This reaction is a natural response of the body to weight loss, as it seeks to maintain what the brain perceives as its “normal” body weight, which may fall within the obese category for some individuals. The newly developed weight-loss medications function by inhibiting this physiological response, thereby facilitating weight loss through dietary and exercise modifications.
In clinical trials, participants receive support for exercise as well as access to dietitians and psychologists. These professionals offer tailored assistance regarding the lifestyle changes essential for optimizing the efficacy of these medications. Such support is rarely available to individuals outside of clinical trials, and its absence may hinder the drugs’ effectiveness if the requisite lifestyle adjustments are not facilitated by these specialists.
Numerous studies have aimed to determine the factors that may predict responses to weight-loss injections. A prevalent factor associated with significant weight loss is a higher initial body weight.
Significant media attention has surrounded the introduction of these new weight-loss injections, leading to a surge in demand among individuals for whom the drugs were intended (those with obesity) as well as among those who are not obese but wish to lose a few kilograms.
In the United Kingdom, the National Institute for Health and Care Excellence (NICE) establishes guidelines regarding the clinical criteria necessary for the prescription of a drug. For Wegovy and Mounjaro, individuals must be classified as obese and have at least one obesity-related health condition, such as sleep apnea or hypertension.
Due to the scarcity of alternative effective weight-loss medications, coupled with extensive media coverage, there have been instances of off-label prescribing of these drugs to individuals who do not meet NICE’s criteria.
A likely outcome of this practice is that individuals with body weights below the recommended guidelines are being prescribed these medications for weight loss, resulting in less weight loss than what was observed in clinical trials.
Despite the small percentage of individuals for whom these medications may not be effective, their introduction holds the potential to deliver substantial health benefits to millions who have previously faced challenges in achieving weight loss.
