Looking beyond the scale: Why measures of physical activity should be incorporated into obesity trials to support long-term sustainable weight loss
Since anti-obesity drugs like GLP-1 receptor agonists, including Ozempic and Wegovy, received regulatory approval, they have evolved from specialised treatments for type 2 diabetes into widely adopted weight-loss solutions, dramatically changing how healthcare professionals approach the treatment of obesity in patients.
These medications target the brain’s appetite and satiety centres to reduce hunger and slow gastric emptying. This can help individuals feel fuller for longer and can promote weight loss. When measured by traditional weight loss metrics, GLP-1 therapies have consistently outperformed other pharmaceutical options and lifestyle interventions and almost match the results of surgical treatments.
Understanding weight loss
GLP-1 medications have multifaceted effects on patient well-being, raising several important questions. One concern is the effect of these treatments on muscle mass. While some muscle mass depletion is inevitable with all weight loss, there are concerns that the decline is much more significant when using these medications. A considerable drop can lead to immediate and long-term harm, since lean mass is critical to overall health and daily functioning. Developing evidence-based guidelines to mitigate these risks will be essential for sustainable obesity treatment.
A further concern is that many patients discontinue GLP-1 therapies after reaching their target weight, which can lead to rapid regain of the lost weight, potentially replaced by fat, rather than regaining lost muscle mass. This issue was highlighted in the STEP 11 and STEP 42 trials. These studies reported significant weight gain once GLP-1 treatment ended. There is also data to suggest that repeated weight loss and regain, known as weight cycling, may increase mortality risk and increase the risk of cardiovascular events.3
Educating patients about the potential adverse effects of these medications and not positioning them as a definitive solution is part of responsible patient care. As the industry progresses and more drug options enter the pipeline, the need for clinical evidence of health benefits beyond short-term weight loss and improved clinical trial designs will be critical in differentiating these treatments and guiding healthcare professionals in decision-making.
The role of physical activity
Physical activity is one of the key factors in sustaining weight loss, preserving muscle mass, and achieving long-term health benefits. It is commonly included in obesity clinical trials. For instance, in the STEP 4 trial,2 patients in the treatment and placebo groups were required to increase their physical activity by 150 minutes per week. Approved GLP-1 medications are indicated explicitly as adjunct therapies alongside lifestyle modifications, which include increased physical activity to maximise their benefits and maintain muscle strength.
In a study by the University of Copenhagen using a multi-armed randomised controlled trial, researchers examined the interaction between GLP-1 medication and physical activity. The findings show that combining medication and physical activity led to more sustainable management of obesity than relying on medication alone.4
These findings demonstrate the importance of patient commitment to regular exercise for ensuring treatment efficacy, especially in preserving muscle and sustaining long-term weight loss. They also highlight the need for drug developers to develop robust data to support the sustainability of medication-assisted weight loss. Furthermore, accounting for physical activity variables within clinical trials will reduce noise in the data, yielding a more comprehensive understanding of treatment effectiveness.
Monitoring physical activity in weight loss trials
In drug development, patients typically self-report physical activity through paper or app-based diaries and questionnaires. However, these self-reported outcomes are prone to inaccuracies and often correlate poorly with the actual amount and intensity of daily physical activity.
Using wearable digital health technologies (DHTs) may help address these challenges and provide a more accurate measure of physical activity. Access to objective and continuous data capture of an individual’s physical activity, such as step count, speed, and duration, can provide an accurate view of their real-world functioning and how this correlates with their achieved weight loss and maintenance.
Wearables can contribute to measures of the quality and intensity of physical activity, including cardiorespiratory fitness, daily moderate-to-vigorous physical activity (MVPA), and sedentary time. It is well understood that walking and the speed of walking improve with muscle strength and cardiovascular fitness and can be predictors of future health outcomes. Wearable technology can passively assess and quantify walking speed and frequency with minimal patient burden. It is now also possible to estimate VO2Max and evaluate patients for sleep apnoea. This can provide data to indicate how obesity treatments impact quality of life.
Wearable technology can provide meaningful clinical endpoints for regulatory approval. Adding these objective measures to clinical trials can help better understand how medication and lifestyle factors influence weight loss and muscle mass, providing more robust data on treatment effects. The next step for the industry is to develop agreed standards on the intensity and frequency of physical activity required of patients to maximise the efficacy of GLP-1 medications while also ensuring muscle maintenance.
In developing guidelines, healthcare professionals will be equipped to provide patients with more practical and evidence-based recommendations to support their weight loss. This could be a key factor in minimising weight cycling and helping individuals reach their goals for the long term.
