Introduction

GLP-1 receptor agonists (GLP-1RA) have become widely discussed in recent years, both in clinical practice and in public media. You might be more familiar with some of the brand names, such as Ozempic/Wegovy (both semaglutide) or Mounjaro (tirzepatide).

Originally clinically effective as antidiabetic agents, their use has been popularised for weight loss in recent years. At times, the online publicity can make them seem like a “magic” weight-loss solution – almost like a “The Nutty Professor” moment, where you wake up after a few doses and see a completely different person in the mirror without the effort of exercise. But this is a misconception. GLP-1s change appetite and metabolism, but they don’t build muscle or maintain metabolic rate. That’s where exercise is essential.

For both diabetes management and weight loss, exercise remains a crucial part of enhancing and maintaining the benefits of GLP-1 therapy. This will be the focus of this article.

Understanding GLP-1s: a gastrointestinal peptide

GLP-1, aka glucagon-like peptide-1, is a protein produced mostly by the L-cells in the small intestine but also in alpha cells in the pancreas, and is typically released after food consumption.^1,2 

GLP-1 receptor agonists (GLP-1RA) are medications that have been developed to mimic natural GLP-1. When released, it acts as a hormone to stimulate GLP-1 receptors and signal to the body to carry out these functions:

• Stimulate insulin secretion – this helps glucose be removed from the blood and used effectively for energy
• Inhibit glucagon secretion – glucagon signals the liver to release stored glucose when needed in healthy people. In people with high blood sugar, stopping its release helps keep down blood sugar levels

Both of these actions ultimately lower blood glucose, known as glycaemic control. It is also involved in metabolic control, including:

• Slowing down stomach emptying – this delays the breakdown of the nutrients in your food, thus reducing post-meal spikes in blood glucose
• Regulating appetite – it contributes to feeling full, hence lowering food intake

Independent of the weight loss, GLP-1RAs have also been found to be directly cardioprotective, and studies have shown a significant reduction in major cardiovascular events, including heart attacks and strokes, with additional anti-inflammatory benefits and even some improvement of left-ventricular function in people with heart failure.^3,4,5

GLP-1RAs bring about these actions to treat diabetes and obesity, with additional benefits for people who have weight-related conditions such as hypertension, cardiovascular disease, or fatty liver disease.⁵ These are major causes of illness and death worldwide, which is why GLP-1 therapy is not simply “cosmetic”, but medically significant.⁶

How exercise helps

Exercise is recognised to have positive health benefits for adults in general, and works as a mainstay of diabetic and obesity treatment by increasing muscle metabolism and improving insulin sensitivity.⁷

Different types of exercise can complement GLP-1 therapy, including;

Resistance (strength) training 

This is intended to maintain or increase muscle mass. It prevents the drop in the body’s energy at rest that can be seen with rapid weight loss, and reduces the risk of weight regain after discontinuing GLP-1s.

Aerobic (cardio) exercise  

This type of exercise has great benefits for heart and lung health, by strengthening the heart muscle and improving circulation. As more energy is expended through this type of exercise, it consistently aids in fat loss.

Flexibility and balance training 

This is a necessary accompaniment to prevent muscular injury and enhance mobility and joint health, especially as the body’s composition changes with the use of GLP-1 medication.

Combining different types of exercise throughout the week can yield significant results and accelerate progress. The body can become subject to plateaus as it gets more efficient with repetitive exercises, which become less of a challenge over time.⁸ Plateaus can also occur with GLP-1s due to the metabolic adaptation caused by substantial weight loss.⁹ Adding variation and including progressive strength training with weights can challenge your body to break through that perceived stagnancy.⁷

Long-term success: why exercise matters with GLP-1RAs

Diabetes

Despite the benefit seen by employing GLP-1s, metabolic control in the long term requires effort beyond medication. In the context of diabetes, exercise enhances overall glycaemic control, including potentially through stimulating the release of the body’s own GLP-1. 

It also improves insulin sensitivity, which is the main issue in diabetes, and improves glucose tolerance.⁷ Therefore, exercise has the effect of “boosting” the medication’s action.

Weight loss

Weight maintenance

Studies show that medication alone is not enough to maintain weight loss. After stopping GLP-1 therapy, weight regain is typical. This happens because the hormonal appetite suppression is no longer active when the medication stops. Without lifestyle changes, you will likely put weight back on.¹⁰ With the addition of exercise, there is evidence that you will be able to maintain a healthy weight for longer after stopping the medication.¹¹

Muscle loss and metabolic slowdown

Another issue is that with GLP-1 therapy, people don’t just lose fat tissue. They also experience loss of lean muscle mass – roughly 25% of total weight loss is comprised of lean muscle unless resistance training is integrated into treatment.⁸ 

As mentioned earlier, this muscle loss also contributes to low energy levels during rapid weight loss, which may explain the fatigue and sluggish feeling some people can experience while on the medication. This is because muscle burns calories even at rest, and losing it slows metabolism, which makes long-term weight regain more likely. 

These risks can be offset by regular exercise and adequate protein intake to ensure preservation of proportionate muscle mass and maintenance of energy levels at rest.^6,9 Keeping the muscles active with training helps maintain metabolism and prevents long-term weight regain.

The combined effect of exercise with medication may allow lower maintenance doses of GLP-1s over time, which can decrease the risk of associated side effects. Seeing progress can be a motivator to keep going and maintain the changes you implement. Overall, combining exercise with GLP-1s provides a synergistic effect, and they work together to yield even better results. 

Common challenges

Gastrointestinal side effects from GLP-1s, including nausea, vomiting, and diarrhoea, are not an uncommon occurrence, especially where dose increases are prescribed.⁴ Speak to your doctor or pharmacist if you are taking a GLP-1 and begin to experience issues like this. It may be a good idea to adjust the timing of exercises relative to the GLP-1 dose if you are sensitive to such effects.

If mobility or chronic pain is a barrier, low-impact options like swimming, cycling, chair exercises, or physiotherapy-guided programs can still provide significant benefits.

Practical tips

• Start gradually– aim for 150 minutes of moderate activity each week, broken down into a routine that works for you. Focus on consistency over intensity. The key reason it fails for some is not that they don’t train hard enough, but that they don’t stick to it over time. The best benefits will come from consistency, so aim to integrate it into your lifestyle
• Incorporate a protein-rich diet to support the maintenance of muscle mass
• No two people are the same – you can work with healthcare professionals, including physiologists and dietitians, for individualised plans suited to your needs
• The scale isn’t the whole picture – as you exercise, the body composition changes. Fat is lost, and muscle is gained, so dropped fat may not always show up on the scales. Track progress with your energy levels, strength, and endurance, not just weight 

Summary

Physical activity boosts the effect of GLP-1RA treatment. Incorporating exercise into the regimen is necessary for effectively treating both obesity and diabetes in the long term. Together, GLP-1 therapy with exercise provides a much more powerful therapy than GLP-1s alone. With physical activity and GLP-1RA treatment, expect amplified, longer-lasting treatment outcomes and greater reductions in the risk of future cardiometabolic diseases.