Clinical trials for weight-loss drugs like Wegovy and Mounjaro have shown impressive results, with participants shedding between 16% and 21% of their body weight. However, not everyone experiences these benefits. Studies have revealed that a significant portion of participants, roughly 10% to 15%, lose less than 5% of their body weight—a threshold considered clinically meaningful. Anecdotal evidence from obesity specialists suggests that outside of controlled clinical settings, up to 20% of users may not respond effectively to these treatments. But why do these drugs work for some and not for others?
The Complex Nature of Obesity
To understand why some people are less responsive to these medications, it’s essential to appreciate the complexity of obesity. Over the past decade, research has highlighted that genetic factors play a substantial role in determining body weight. A study published in 2021 revealed that 0.3% of the UK population—roughly 200,000 individuals—carry a genetic mutation that disrupts the brain’s regulation of appetite. This genetic variation leads to an average of 17kg of additional weight by the age of 18. Such genetic predispositions may explain why certain individuals do not experience the same level of weight loss despite using these drugs.
How Weight-Loss Injections Work
The effectiveness of weight-loss injections like Wegovy and Mounjaro is rooted in their ability to counteract the body’s natural defenses against weight loss. When people attempt to lose weight through diet and exercise, they often encounter increased hunger and fatigue. This response is a survival mechanism that prompts the body to maintain its “set point” weight, which, for some individuals, may fall within the obese range. These drugs work by suppressing this physiological response, making it easier to lose weight through controlled dietary changes and exercise.
However, the clinical success of these treatments is often linked to additional support provided during trials. Participants in clinical studies receive access to dietitians, psychologists, and exercise experts who offer personalized guidance to help them adapt their lifestyle and maximize the drugs’ effectiveness. Outside of clinical trials, many people lack this kind of comprehensive support, which may reduce the overall success rate of the medications in real-world settings.
Predictors of Success
Research has sought to identify factors that might predict a successful response to weight-loss drugs. One common determinant of success is a higher starting body weight. In general, individuals with more significant obesity tend to lose more weight with these treatments. For people with lower body weights or less obesity, the drugs may not produce the same degree of weight loss, which could explain why some users report minimal results.
The Role of Media and Demand
The media buzz surrounding Wegovy and Mounjaro has fueled a surge in demand, with many individuals eager to try these medications—not just those with obesity, but also those who are merely looking to shed a few extra kilograms. In the UK, the National Institute for Health and Care Excellence (NICE) has established strict guidelines for prescribing these medications, limiting their use to people with obesity who also have at least one obesity-related health condition, such as high blood pressure or sleep apnea.
Despite these regulations, reports have emerged of doctors prescribing these drugs off-label to individuals who do not meet the official criteria. This off-label use often involves patients with lower body weights, who are less likely to achieve the significant weight loss seen in clinical trials. Consequently, these individuals may experience diminished results compared to those for whom the drugs were originally intended.
The Bottom Line
While the efficacy of weight-loss drugs like Wegovy and Mounjaro is not universal, their introduction marks a promising shift in the fight against obesity. For many people who have struggled with traditional weight-loss methods, these medications offer a new opportunity for meaningful health improvements. However, their effectiveness is influenced by a range of factors, from genetics and starting body weight to access to expert support and adherence to prescribing guidelines. Understanding these variables can help set realistic expectations for those considering these treatments.
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