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Understanding Obesity Medications and the Role of Exercise

Obesity medications are a hot topic. But how does exercise play into their use and their effectiveness? Read on to find out!

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It’s hard to go a day without hearing or reading about obesity medications, whether it be through social media posts or online articles, and you might even find yourself humming some of the catchy commercial jingles for these medications. There is no doubt that the popularity of obesity medications has taken America—and much of the world—by storm over the last year. The issue is wading through all the information that is out there and not allowing opinion and biases to cause you to drown. So what does this mean for the fitness industry? I am sure many of you have asked yourself this question already, and some may have already formed an opinion. 

It is especially important for fitness professionals, that have long played a critical role in supporting clients on their weight management journeys, to have an understanding of these therapeutics This understanding includes how they work, are indicated and medically managed, and the role exercise plays for clients on these effective agents. This article provides an overview for fitness professionals based on the scientific evidence to help you critically evaluate what you read and hear going forward, so you can create effective and personalized programs for your clients who are taking these pharmacotherapy agents. 

Understanding Obesity as a Disease 

Before we get started, let’s be clear— these medications are approved by the Food and Drug Administration (FDA) for the treatment of obesity, and not for modest weight loss (FDA 2023). This is a really important distinction, as headlines across the globe like to refer to these as “weight loss” drugs. These medications are not meant for short-term weight reduction, but for the long-term management of the disease of obesity. In 2013, the American Medical Association classified obesity as a chronic disease.  

While the use of body weight is used to monitor treatment effectiveness, and body mass index (BMI) is used as an initial indicator of potential risk, when we refer to obesity as a disease, the number on the scale is actually only one marker of this complex state of biological dysfunction. Obesity occurs when there is dysregulation in the body’s biological systems that ultimately impact food intake and control the body’s set point weight level. Dysregulation can occur in parts of the brain responsible for signals of hunger, appetite, reward, and when it is time to stop eating (Berthoud Münzberg & Morrison 2017). What causes this dysregulation, and why are some people more susceptible to obesity? Obesity is caused by both genetics and the environment, and the interaction between them (Berthoud Münzberg & Morrison 2017; Purnell 2023). For these complex reasons and others, the medical management of obesity has evolved to include pharmacotherapy agents, and also metabolic/bariatric surgeries, to help level the biological playing field. 

But what about lifestyle? Does the strategy of “eating less and moving more” treat obesity? While this approach can absolutely impact body weight to a certain degree, changing diet and exercising does not assist with the underlying biological factors of obesity—those that make maintaining body weight loss in the long-term so difficult. When we go back to the mechanisms of obesity, we find that the body adapts to weight loss and then biology turns on mechanisms that stimulate weight regain through increases in hunger and appetite signaling (Garvey 2022). Therefore, while participating in behaviors such as exercise and healthy eating can positively impact health and well-being, the long-term management of obesity with lifestyle modification (only) can be difficult for persons living with the disease.  

We must respect that living with obesity and treating obesity are not simple, and people do not choose to live with obesity. Historically, people have believed that obesity is caused by “not choosing” to eat a healthy meal, or “not choosing” to do a workout. But remember, some of the choice is being controlled by biology and not just a person’s behavior. So does that mean that persons with obesity should not exercise or modify their eating habits? Absolutely not! It may just mean that we need to reframe the role that exercise and lifestyle play in this new age of obesity treatment.  

Understanding Obesity Medications 

Knowing the landscape of obesity medications can feel daunting and can be hard to keep up with. In fact, it is recently estimated that there are between 75-100 new pharmaceutical agents in the research and development pipeline. To break the space down, below are some common questions and responses about how obesity medications work, are indicated and administered.  

How does Ozempic® work? 

First off, let’s pause and talk about the correct names of obesity medications before we dive into how they work. The type of obesity medications that have recently come into popularity due to their high level of effectiveness are Semaglutide and Tirzepatide. These medications are a class referred to by a few different names that all describe what they do in the body. They can be called incretin-based therapies or incretins, or nutrient stimulated hormone therapies (NuSHs), or simply GLP-1s. Glucagon-like peptide-1 or GLP-1 is a type of “incretin,” or “nutrient-stimulated hormone” in the body, that these medications mimic and go on to target the hormone’s receptor in the body. With obesity, there can be disruption in NuSH signaling as a result of underlying metabolic dysfunction. These medications target NuSH(s) receptors in the brain that help control hunger and appetite signals and also slow gastric emptying, which helps people feel fuller longer. 

But what about their names? Why not call them all Ozempic®? Here’s the trick, you need to understand that these medications were first approved for the treatment of type 2 diabetes because of their ability to increase insulin secretions from the pancreas. Once it was determined that there were also significant changes in body weight, these agents were further studied for the treatment of obesity. Most people consider these to be new medications; however, Liraglutide—an earlier GLP-1 based medication—was first approved for the treatment of type 2 diabetes in 2010 (Victoza®), and then later approved for obesity treatment in 2014 (Saxenda®). Ultimately, there have been studies of this class of agents for the last 20 years. 

Semaglutide and Tirzepatide follow similar approval patterns. Semaglutide was approved for type 2 diabetes under the tradename Ozempic® in 2017, and later approved for obesity treatment as Wegovy® in 2021. Tirzepatide was approved for type 2 diabetes (Mounjaro®, 2022) and then obesity treatment, (Zepbound®, 2023) and was the first medication in this class to target an additional NuSH, called GIP or glucose dependent insulinotropic peptide. With that, calling all of these medications “Ozempic®” is problematic so fitness professionals should refer to these medications by their proper name, whenever possible. It is also important to note that there are other earlier generations of obesity pharmacotherapy (not GLP-1-based therapies) that are FDA approved and still utilized by healthcare providers to treat obesity. 

Why are these medications so popular? Do they cure obesity? 

Even though Liraglutide has been around for a while, everything changed when Semaglutide was approved for obesity treatment in 2021. That’s because it was observed for the first time that an obesity medication improved the magnitude of weight loss that is typically seen with lifestyle treatments (diet and exercise). Typically, intensive behavior weight loss interventions—that include reducing caloric intake and increasing moderate-to-vigorous physical activity—can achieve weight losses of on average 8-10% in 24-52 weeks (Jakicic et al. 2016; Jakicic et al. 2018; Jakicic et al. 2022). Contemporary obesity medications have improved on those numbers. The phase 3 clinical trial of Semaglutide demonstrated approximately a 15% weight loss after 68 weeks (Wilding et al. 2021), which is also double the weight reduction compared to what is achieved with Liraglutide (Rubino et al. 2022). Tirzepatide, the dual GLP-1/GIP receptor agonist (which binds and activates the receptors), produced on average the largest magnitude of weight loss of the pharmacotherapy agents at approximately 20% after 72 weeks (Jastreboff et al. 2022) . Beyond obesity treatment, these medications are demonstrating to be highly effective at treating and preventing future type 2 diabetes and cardiovascular events, and reducing obstructive sleep apnea. 

These medications do not cure obesity, they help treat the underlying biological dysregulation associated with obesity that was described earlier. Like many treatments, there is a chance of experiencing a plateau, there is also variability in who responds to the medications, and variability in the magnitude of weight lost. This is why obesity is such a complex disease to treat; some treatments and medications work for some patients, and other treatments don’t. This is important to consider because although the headlines and business analysts like to boast that these are “game changers” and “magic bullets” for weight loss, that isn’t the case for everyone. That is why appropriate medical management in conjunction with a healthcare provider is key. There is no such thing as a one-size fits all approach when it comes to obesity treatment. Lastly, because these agents are helping treat the underlying biology associated with obesity, there is evidence to show that once they are stopped, patients will being to regain weight; thus, they are currently recommended for long-term use (Rubino et al. 2021). 

Who can take these medications? 

The medications are indicated for patients with obesity, i.e., those with a BMI greater than or equal to 30 kg/m2. Patients that have a BMI greater than or equal to 27 kg/m2 that also have an obesity-related co-condition, like type 2 diabetes or hypertension, can also be treated with these contemporary obesity agents. While BMI is used to help screen for eligibility, it is not the primary indicator of whether or not pharmacotherapy is appropriate for a patient. The decision to use these agents occurs between the healthcare provider and patient after comprehensive medical screening and discussions (Burridge et al. 2022). Lastly, it is important to consider that not all insurance plans cover medications for obesity treatment.  

How are these medications taken? What are the side-effects? 

For obesity treatment, GLP-1-based medications currently approved are self-administered with a subcutaneous injection into the abdomen, thigh or upper arm. Liraglutide is injected daily, while Semaglutide and Tirzepatide are administered 1x per week. Some of the many agents currently being tested for future approval are working to create oral forms of these agents, use different NuSH combinations, and reduce the frequency of injection. 

These medications are initially administered at the lowest dose and slowly increased, as determined to be appropriate by the overseeing healthcare provider based on what is tolerated by the patient. Common mild-to-moderate side effects with taking these types of medications are related to gastrointestinal discomfort—a generalized term that includes nausea, vomiting, constipation, diarrhea, and/or abdominal discomfort or pain. There is also a chance of hypoglycemia (mostly in patients with type 2 diabetes), and there may be an increase in resting heart rate. Healthcare providers will screen for other health conditions ahead of prescribing a GLP-1-based therapy. 

Who manages these medications and how do clients get these medications?  

Just like with any other chronic disease, medications for obesity treatment are to be prescribed and medically managed by a healthcare provider. preferably one that specializes in obesity medicine (American Board of Obesity Medicine, DABOM). Importantly, the ideal provider knows the patient and will complete a thorough screening and medical history before determining the appropriate obesity treatment strategy, which may include pharmacotherapy. Given the complexity of obesity treatment, regular follow-up and medical monitoring of progress and side effects are critically important in order to provide the patient the best treatment and care possible (Burridge et al. 2022). Fitness professionals should be cautious of getting involved in operations that are selling compounded versions of semaglutide and tirzepatide direct-to-consumer without appropriate and long-term medical care and oversight, as previously described. The Obesity Action Coalition, The Obesity Society, and The Obesity Medicine Association have released a joint position statement on the use of compound medications, and the FDA also has released information on compound semaglutide.  

Now that these drugs are helping control appetite, what is the role of lifestyle?  

Of importance, the FDA has approved these medications as an adjunct to healthy lifestyle changes, which include eating a reduced calorie diet and increasing physical activity. Beyond the indication label, exercise professionals will continue to remain an important part of the obesity treatment team. Now that you have a better understanding of how these agents work, we can ’move on’ to discuss more about exercise for clients who are taking these contemporary obesity medications.  

Repositioning Exercise for Clients Taking Obesity Medications 

Watching the fitness industry’s response to this new age of obesity medications has been eye-opening, as both an exercise physiologist and as an obesity researcher. The spectrum of responses spanning from… 

People being completely opposed to pharmacotherapy for obesity treatment; hearing statements from popular trainers and fitness pros like, “You don’t need to be on those medications. You need to get at the root cause and change your diet and exercise habits.” 

 to… 

Jumping all-in (maybe too quickly) and building targeted businesses around GLP-1s.  

Two very different extremes, each with their own considerations and cautions. It is okay to have personal feelings about the use of obesity medications; however, one should not overlay those biases onto clients that have made a decisions with their healthcare provider to take an obesity medication. It is outside of our scope of practice as fitness professionals to advise clients whether taking a medication is appropriate for them or not. Our role is to support them on their obesity treatment journey as it relates to engaging in exercise behaviors (more on this in the next section). On the other extreme, there are mixed feelings over the push to “bring GLP-1s to fitness centers,” or the mass marketing that is happening around “building GLP-1 programs.” It is encouraging to see the fitness industry embracing options for persons with obesity; however, there are also concerns with scope of practice and liability for fitness professionals and owner/operators, and importantly, allowing for appropriate medical management for the client/patient (which is necessary with these medications). Additionally, we have very little research to date on the role of exercise with agents like semaglutide and tirzepatide. There is still much to learn and as stated previously, one-size fits all programming does not work for the complex disease of obesity. 

So are we jumping the gun? Maybe. But patients are being prescribed these agents and becoming our clients, so let’s dive into what we do know and don’t know about exercise and GLP-1 medications.  

Can we program for clients who are using obesity medications by following the weight management/weight loss guidelines? The recommendation is no. With lifestyle-only  interventions (i.e., diet and exercise) for obesity treatment, the recommendation has been focused on programming upwards of 200-300 minutes per week of moderate-to-vigorous aerobic activity, to maximize energy expenditure/caloric burn (Donnelly et al. 2009; Jakicic et al. 2001). Now that these obesity medications are assisting with appetite regulation and helping clients eat less overall, it may be appropriate to refocus programming away from maximizing caloric burn. In two recent publications (Jakicic Rogers & Church 2023; Jakicic Rogers & Apovian 2024), my colleagues and I recommend repositioning activity to help clients taking a medication feel and function their very best, opening the door for more person-centered and individualized programming. 

Recommendation 1: Move away from high-volume aerobic activity with a focus of programming for energy expenditure. Refocus on the personal goals of the client you are working with.  

What do we know about the specific needs of clients taking obesity medications? This is where we are just getting started in the research. Currently, there is no published data on exercise tolerability with Semaglutide and Tirzepatide, but the following are some key considerations related to exercise that we have learned from conducting qualitative research interviews with patients taking Semaglutide or Tirzepatide.  

Weakness and Fatigue: some patients taking these agents report feeling fatigue or weaker after starting a GLP-1-based medication even though they have lost weight. These are definitely relevant targets to focus on. Our initial data also demonstrates that those patients who are engaging in exercise do not necessarily experience fatigue, suggesting that exercise may play an important role in energy levels for patients taking these agents (publication in review). That makes complete sense, as we know well the impact that exercise training can have on fitness and energy levels with both acute and chronic training. 

Recommendation 2: For clients reporting fatigue, target programming to improve cardiorespiratory fitness as appropriate.  

But what about weakness and what everyone seems to be talking about…the loss of muscle mass? While weakness may be a relevant target based on what we have heard from patients, we should be careful to not jump to conclusions about muscle mass and the impact exercise might have on muscle mass changes. Let’s break it down based on what we know and don’t know yet from the research… 

  • Currently, we have estimates that contemporary GLP-1 medications may be reducing lean mass between 25-40%, which is greater than what we see with lifestyle interventions (Wadden et al. 2023).  
  • We need to remember that lean mass is not the same as muscle mass and these terms should not be used interchangeably. Muscle mass is one component of the lean mass compartment, which includes muscle, bone, water, organs and all other tissues. 
  • There is currently no published data on exactly how much muscle is specifically lost when taking Semaglutide or Tirzepatide (good news, we currently have studies underway to examine changes in body compositions, and specifically muscle mass). 
  • It is important to remember that any time there is weight loss with caloric restriction, there is likely lean muscle loss, especially in hypocaloric state where there are fewer than 1000 kcal per day being consumed. A great example for comparison comes from the very low-calorie diet studies that had exercise components. These studies demonstrated that even with resistance and/or aerobic training, there were decreases in lean mass with weight loss after 3 months. Lean mass was not preserved. However, the good news is that resistance training produced improvements in strength and aerobic training increased cardiorespiratory fitness even when lean mass was lost (Donnelly et al. 1991; Donnelly et al. 1994).  

As we think about developing recommendations and building themed programs around “muscle mass loss and GLP-1s,” the recommendation is to proceed with caution. We do not (yet) have evidence that resistance training will “preserve” or “slow” muscle mass loss, and we do not know exactly how much muscle is lost on GLP-1 medications. However, encouraging clients to exercise for muscle health, to improve physical function, and to enhance quality of life and strength is more appropriate—and a relevant target given the current state of the evidence (Jakicic Rogers & Church 2023; Jakicic Rogers & Apovian 2024; Rogers 2024). 

Recommendation 3: Do not make claims that resistance training programs will preserve muscle mass loss when taking a GLP-1-based medication. Instead prioritize building person-centered, not method-centered, programs based on the needs and goals of the client on their obesity treatment journey. 

Tailor programs to the person you are working with is the overall recommendation; however, there are a few key concepts specific to clients taking obesity medications that you should be aware of: 

  1. Side-effects. Once a client has shared that they are taking an obesity medication, first thank them for sharing this information with you, then be sure to ask for their permission to discuss any side-effects that they may be having. This is not for the purpose of counseling on their medical treatment decisions, but instead so you can program appropriately with these side-effects in mind. For example, it might be important to know when their injection day is because some patients experience greater side-effects on that day. Additionally, encourage clients to share with you when they have a dose change, as their side-effect profile may change and subsequently impact their ability to engage in exercise.  
  1. Eating patterns. Without crossing outside our scope of practice, we need to be aware that our clients taking obesity medications are not as hungry anymore; however, we want to make sure that they have enough fuel to perform their exercise safely and effectively. This includes watching for signs and symptoms of hypoglycemia.  
  1. Ask about their experience with exercise. Do not assume that your clients have never exercised before. In fact, many patients that I have interviewed stated that they have tried every method or program out there to lose weight— they aren’t coming to you for your method, they are coming for a personalized program. It is also important to realize that you may have some clients that have not engaged in structured exercise, and as a result they may have fears and concerns coming into a gym or working with a trainer.  
  1. Update and check-in regularly. This is new territory for the fitness industry, and remember, your client may be going through a lot of changes as well. Create a safe space for your client to feel comfortable updating you on their progress, and be prepared to refer your clients for psychological or medical care as needed when concerns fall outside of your scope of practice.  
  1. Be prepared to make modifications. Remember, a one-size fits all program will likely not drive long-term engagement in this population. Tailor the program to the person, and make modifications based on the day.  

This new era of obesity treatment is exciting and there are still a lot of unknowns, information to learn regarding the role of exercise, and there may even be new pharmacotherapy agents in the future. Exercise professionals are well positioned to be key members of the obesity treatment team, but that requires collaborating with medical providers and other allied healthcare professionals (registered dietitians, behavioral psychologists, etc.) that work together on obesity care teams. Most importantly, building a trusting and positive environment for clients with obesity needs to be a number one priority, so they have access to an exercise professional that is there to support—and not judge—them on their obesity treatment journey. 

Want to learn more? Programming for Exercise and Medications and Exercise and Chronic Medical Conditions

References

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