In recent years, anti-obesity drugs have surged in popularity, with brand names like Saxenda, Mounjaro, Zepbound, and Xenical becoming household names. With obesity levels rising globally, affecting over 1 billion people worldwide according to the World Health Organization (WHO), it’s no surprise that many people are turning to these medications as a potential solution. The UK has seen a particularly sharp increase in the prescription of these drugs, with data from the NHS indicating a 65% rise in obesity medication prescriptions over the past five years.
For many, these drugs seem like a quick fix, a magic pill to melt away excess weight without the gruelling effort of lifestyle changes. And while they do offer clinically significant weight loss, the question remains, are they enough? Can a prescription alone truly tackle obesity, or is there more to the story? A recent systematic review with meta-analysis delves into this issue, exploring how combining anti-obesity drugs with exercise training might be the key to sustainable weight loss and better health outcomes.
The Study
A research team comprising Bruna Marmett, Igor da Silva, Fabio Lira, and Gilson Dorneles conducted a systematic review and meta-analysis titled: Anti-Obesity Drugs Alone or Combined with Exercise Training in the Management of Obesity (Marmett et al., 2025). Published in the journal Translational Exercise Biomedicine, this study sought to compare the effects of anti-obesity drugs alone versus anti-obesity drugs combined with exercise training. The goal was to determine how these two approaches influenced body weight, body fat, fat-free mass, and cardiorespiratory fitness in obese individuals.
How Was the Study Conducted?
The researchers conducted a systematic review of randomised clinical trials (RCTs), gathering data from four studies with a total of 202 participants. These individuals were all classified as obese (BMI >30 kg/m²) but did not have type 2 diabetes. The anti-obesity drugs assessed included Orlistat (Xenical/Alli), Liraglutide (Saxenda), and Tirzepatide (Mounjaro/Zepbound). Some participants used these medications alone, while others combined them with structured exercise training.
The primary outcomes assessed were changes in body weight, body fat, fat-free mass (muscle retention), and VO2Peak (a measure of cardiorespiratory fitness). The GRADE approach was used to assess the quality of evidence, ensuring robust and reliable conclusions.
So Are Anti-Obesity Drugs Enough?
The findings were clear but nuanced. While anti-obesity drugs alone do contribute to weight loss, their effects are significantly improved when combined with exercise. Let’s break down the key results:
Weight Loss: More Effective with Exercise
- Orlistat combined with exercise resulted in an average weight loss of 2.27 kg more than Orlistat alone.
- GLP-1 receptor agonists (Liraglutide, Tirzepatide) combined with exercise led to an average of3.96 kg greater weight loss than the drug alone.
- The overall trend showed that exercise enhanced the weight loss effects of anti-obesity drugs, making them more effective in real-world application.
Fat Mass Reduction: Drugs Help, But Exercise Enhances It
- Orlistat + exercise reduced fat mass by 2.89 kg more than Orlistat alone.
- GLP-1 receptor agonists + exercise reduced fat mass by 1.76 kg more than the drugs alone.
- These results reinforce the fact that exercise is crucial for optimising fat loss rather than just overall weight loss.
Fat-Free Mass (Muscle Retention): Exercise Prevents Muscle Loss
- A major downside of pharmacological weight loss is muscle loss.
- Orlistat + exercise preserved 0.56 kg more fat-free mass compared to Orlistat alone.
- GLP-1 receptor agonists + exercise resulted in a marginal increase in fat-free mass (+0.50 kg), but evidence certainty was low.
- This highlights the importance of resistance training and exercise alongside medication to maintain muscle health.
Cardiorespiratory Fitness (VO2Peak): Exercise is Essential
- Drugs alone showed minimal to no impact on fitness levels.
- Orlistat + exercise improved VO2Peak by 2.64 mL/kg/min.
- GLP-1 receptor agonists + exercise improved VO2Peak by 2.47 mL/kg/min.
- This suggests that exercise remains essential for cardiovascular and metabolic health, regardless of weight loss goals.
What This Means for Us
When working with clients using anti-obesity medications, the key takeaway is that exercise is not optional, it’s essential. To best support clients, implement a structured exercise plan that includes both resistance training and aerobic workouts. Resistance training helps preserve lean muscle mass, which is often lost during weight reduction, while aerobic exercise improves cardiovascular health and metabolic efficiency.
Encouraging progressive overload in strength training (e.g., increasing resistance over time) ensures clients maintain strength and functional fitness. For cardiovascular fitness, interval training or steady-state cardio can be tailored based on individual fitness levels.
Also engage in open conversations about realistic expectations regarding weight loss drugs. Providing education on the benefits of exercise beyond weight loss, such as improved mood, energy levels, and long-term weight maintenance, can enhance adherence. Sharing case studies or testimonials from individuals who have successfully combined exercise with medication could further reinforce the importance of an active lifestyle. Here’s how they can help:
- Educate Clients on the Role of Exercise:Many clients may believe that taking Saxenda, Mounjaro, or Xenical eliminates the need for physical activity. However, educating them on the benefits of muscle retention, fat loss, and improved fitness can help change this mindset.
- Incorporate Resistance Training: Since weight loss drugs often lead to muscle loss, resistance training is crucial. Encourage progressive strength training to maintain lean mass and metabolic health.
- Highlight Cardiovascular Health: Weight loss alone does not necessarily mean improved heart health. Ensuring clients engage in aerobic exercise will help boost VO2Peak, lower cardiovascular risk, and improve overall wellbeing.
- Address Unrealistic Expectations: Some clients may believe that taking a weekly GLP-1 injection will be a permanent solution. Helping them develop sustainable habits will increase long-term success and prevent weight regain.
A Balanced Approach is Best
While anti-obesity drugs have transformed weight management, they are not a standalone solution. The study findings make it clear that while these medications aid in weight loss, exercise significantly enhances their effects by promoting fat loss, preserving muscle mass, and improving cardiovascular fitness. Without physical activity, individuals may experience muscle loss and limited metabolic improvements, reducing the long-term effectiveness of weight loss medications. The evidence is clear, exercise significantly enhances weight loss, preserves muscle, and improves fitness. The growing reliance on medications like Saxenda, Mounjaro, and Xenical should be met with an emphasis on lifestyle interventions.
This presents an opportunity to guide, educate, and support clients, ensuring they get the most out of their weight loss journey. By integrating structured exercise programs, they can help clients achieve not just weight loss, but long-term health and fitness.
References
Marmett, B., da Silva, I., Lira, F., & Dorneles, G. (2025). Anti-obesity drugs alone or combined with exercise training in the management of obesity: A systematic review with meta-analysis. Translational Exercise Biomedicine. Click here to review the full research article.
NHS Digital (2024). Statistics on Obesity, Physical Activity and Diet, England 2024. Available here.
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