Exercise for Clients Taking an Anti-Obesity Medication

Introduction

Reducing obesity and its health consequences remains an important public health priority given the consistent rise in obesity prevalence (1). The consumer market for weight loss was recently estimated to be a 72.6-billion-dollar industry. The landscape of obesity treatment changed dramatically when the Food and Drug Administration (FDA) approved semaglutide, which produces nearly twice the weight loss as previous medications of the same class (2). Since then, the use of contemporary anti-obesity medications (AOMs) has increased, which is also reflected by enhanced media attention, consumers have become well-versed in the popular trade names of AOMs, and health companies and fitness facilities are developing programming around these agents.

Sidebar: Popularity of AOMs

• 2+ Billion: Number of hits on a Google^™ search of “weight loss medications”

• 70+: Number of AOMs in development

• ~3.5 million: Number of Americans prescribed a GLP-1-based medication in 2022

• 300%: Increase in GLP-1 prescriptions since 2020

• 2023: Year Science names GLP-1 medications for obesity its “breakthrough”

It is important for exercise professionals to have a deeper understanding of the effectiveness and indications of these medications, along with the opportunities that these present for patients with obesity and the exercise industry.

Obesity as a Disease

Contemporary AOMs are approved to assist with the complex disease of obesity. The American Medical Association declared obesity a disease, and states in its policy that “the multiple pathophysiological aspects require a range of interventions to advance obesity treatment and prevention.” This is justified given the complex collision of biology, behavior, and environmental factors that contribute to obesity (3).

While the traditional “eat less and move more” framework can be effective for moderate weight loss, long-term obesity care may require additional medical management to assist with the underlying biology. This includes treatments such as bariatric surgery and/or AOM therapy. A contemporary policy on obesity treatment shifts the perspective from curing obesity to it being managed long-term like other chronic disease (type 2 diabetes, high blood pressure, etc.) from a multi-disciplinary team. Exercise professionals are key members of this team.

How AOMs Work in the Body

The contemporary AOMs receiving heightened attention are referred to as nutrient-stimulated hormone (NuSH) therapies. Despite the recent rise in popularity, NuSH therapies are not new and were originally approved for the treatment of type 2 diabetes. After realizing these agents also reduced body weight, they were further studied and approved for obesity treatment. Early NuSH therapies were dulaglutide and liraglutide, and the newest generation includes highly effective semaglutide and tirzepatide. Table 1 shows the generic and trade names of these medications.

Table 1.

Summary of Nutrient-Stimulated Hormone (NuSH) Medications

Generic Name	Administration		Trade Names		Receptor Agonist Type (NuSHs)
	Method	Frequency	Approved for Type 2 Diabetes (FDA Approval Date)	Approved for Obesity (FDA Approval Date)
Dulaglutide	injection	1x per week	Trulicity® (2014)	- NA -	Single (GLP-1)
Liraglutide	injection	daily	Victoza® (2010)	Saxenda® (2014)	Single (GLP-1)
Semaglutide	injection	1x per week	Ozempic® (2017)	Wegovy® (2021)	Single (GLP-1)
	oral tablet	daily	Rybelsus® (2019)	- NA -	Single (GLP-1)
Tirzepatide	injection	1x per week	Mounjaro® (2022)	Zepbound® (2023)	Dual (GLP-1, GIP)

Naturally occurring NuSHs signal the brain and play a role in energy balance that ultimately controls whether the body is storing or burning energy. This can impact food intake, hunger, and cravings. With obesity, there is often underlying metabolic dysfunction that causes disruption in NuSH signaling. These new medications, also called receptor agonists, are effective because they mimic NuSHs and target their receptors in the brain which can reduce hunger levels, slow gastric emptying, and help people feel fuller longer. As a result, people that respond to these AOMs typically eat less and lose weight.

Semaglutide is a single receptor agonist because it targets only GLP-1 (glucagon-like peptide 1) receptors, whereas tirzepatide is a dual receptor agonist; it targets both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide). Impacting more than one NuSH receptor may explain larger weight losses observed in dual agents compared to those that target a single receptor. Table 1 highlights the receptor agonist classification and how each AOM is administered. New agents in development include single, dual, and triple NuSH receptor agonists administered orally, by injection, and at different doses and frequencies (4).

Sidebar: Effectiveness of Contemporary AOMs

STEP-1 (Semaglutide) (5)

This clinical trial randomized 1961 participants into two groups, 1) Semaglutide (2.4mg) + Lifestyle, and 2) Lifestyle only. After 68 weeks, Semaglutide + Lifestyle had a 14.9% reduction in body weight compared to 2.4% in Lifestyle only.

SURMOUNT-1 (Tirzepatide) (6)

Randomized 2539 participants into three groups receiving 5mg, 10mg, and 15mg of tirzepatide compared to a fourth group that took a placebo. All participants received lifestyle counseling for diet and exercise throughout study. After 72 weeks, percent weight loss increased as dose of tirzepatide increased producing weight losses of 15.0%, 19.5%, and 20.9%, respectively. The placebo group lost 3.1%.

Researchers and practitioners that utilize lifestyle programs for weight reduction have questioned the intensity of the lifestyle interventions in the above clinical trials. To put it in perspective, compared to a recent clinical trial of a more intensive lifestyle intervention that modified dietary intake with varying doses of physical activity (150–250 minutes per week), after 52 weeks, weight loss was on average 10% (7). For the first time, contemporary AOMs appear to be more effective, specific to weight reduction, than intensive lifestyle interventions.

Indications, Administration, and Side-Effects

Who can take semaglutide or tirzepatide?

• Adults with a body mass index (BMI) at 30 kg/m² or above, or a BMI at 27 kg/m² or above plus a comorbidity, such as type 2 diabetes or hypertension.

• Children aged 12–18 years with a BMI in the 95th percentile or higher for their age and sex (semaglutide only).

How is it administered?

• For the treatment of obesity, semaglutide and tirzepatide are taken once weekly with a self-administered injection into the stomach, upper arm, or thigh (see Table 1).

• A clinician will prescribe AOMs at a low dose and slowly increase the dose overtime as clinically appropriate and tolerated by the patient.

What are the typical side effects?

• With both semaglutide and tirzepatide, mild-to-moderate gastrointestinal side-effects are reported including nausea, diarrhea, constipation, abdominal pain, and/or vomiting.

• Hypoglycemia (low blood sugar) has also been reported in patients, primarily those with type 2 diabetes, treated with these medications.

Do these medications need to be taken long-term?

• These medications are FDA approved for the treatment of obesity (and type 2 diabetes), not for quick, temporary weight loss.

• There is evidence that once an AOM is stopped, even with an adjunct lifestyle program, patients regained 6.9% of the weight lost (8).

• Stopping an AOM results in hunger returning and patients feeling less full which can lead to increased intake.

Who should determine if an AOM is indicated?

• A clinician, preferably American Board of Obesity Medicine certified, who specializes in comprehensive obesity treatment plans, knows the patient’s medical history, and will continue to monitor the patient on the medication regularly.

• AOMs should be filled by prescription through a certified pharmacy.

• Medication shortages and popularity can lead to the development of compound agents and high-yield operations.

  • Compound forms of NuSH therapies can result in unanticipated side-effects.

  • The FDA recently issued a warning regarding the safety and effectiveness of non-approved agents.

What about lifestyle?

• The FDA approved both semaglutide and tirzepatide with the following indication, “as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management...”

Most board-certified obesity clinicians who prescribe AOMs may refer to these as being an additional tool in the obesity management toolbox. This is because AOMs only impact how much you eat, not how well. Moreover, AOMs are not causing patients to move more. In a recent survey conducted by our group, most patients taking an AOM reported that being physically active was important. However, only 34% achieved greater than or equal to 150 minutes of physical activity per week.

AOMs are intended to be part of a comprehensive care plan that includes regular healthcare oversight and a personalized, multi-faceted lifestyle program that incorporates a physical activity and healthy eating strategy. Having support from a health coach or clinical psychologist can help patients cope with underlying feelings and problems related to their chronic disease.

The Opportunity for Fitness Professionals

Within the context of traditional obesity treatment, the exercise prescription has been focused on increasing energy expenditure, or calories burned with and without dietary modification to change the number on the scale. This has resulted in the recommendation of high doses of physical activity to assist with weight loss and maintenance (9).

The large amount of weight loss achieved with semaglutide and tirzepatide may result in exercise having less impact to enhance weight loss substantially beyond what is achieved with these AOMs. However, this presents an exceptional opportunity to reframe the way that exercise is prescribed for patients taking contemporary AOMs. Exercise prescriptions can move away from dosing activity in terms of calories burned and focus on personalized programming relevant for patients taking an AOM (10).

Currently, there is limited research to understand how physical activity impacts the effectiveness of AOMs (11). Yet, there is an abundance of evidence supporting the independent effects of exercise on health. However, this may require exercise professionals to reposition physical activity to the patient as an important adjunct to their obesity care (12). The following outlines relevant targets for exercise professionals to consider when working with clients taking an AOM.

Programming Considerations:

Body Composition.

There is a concern over the amount of lean mass lost when receiving treatment with an AOM. Recent estimates show a 25% to 40% loss in lean mass when taking contemporary agents (11). While the amount of lean mass lost is greater than that observed in traditional lifestyle interventions (~15% to20%), it is important to remember the following:

• Weight loss is typically accompanied by a loss of lean mass. This is expected.

• In clinical trials with high doses of aerobic and/or resistance training, lean mass loss is not completely preserved in a reduced caloric state.

• The term “muscle mass” should not be used interchangeably with “lean mass.” Muscle mass is only one component of what makes up lean mass that also includes water, bone, organs, and other body tissues.

Currently, research is underway to determine the specific volume of muscle mass lost, and the impact exercise has on muscle mass in patients taking AOMs. Until this work is completed, exercise professionals should avoid promoting that exercise will “preserve muscle mass” when used as an adjunct to contemporary AOM therapies. Patients taking AOMs report feeling weaker; thus, evaluating and programming for improvements in strength and physical function are relevant targets. Research shows that when dieting, resistance training can improve strength and muscle tissue quality, even when lean mass is not completely preserved (13).

Aerobic Fitness.

Patients who participated in our survey reported feeling more fatigued even after losing weight when taking an AOM. This signals that increasing aerobic fitness may be an important target because it is associated with improved energy levels. Interestingly, a clinical trial of liraglutide showed that only the participants that performed aerobic exercise had improvements in fitness (14). Muscle quality (cross-sectional area, mitochondrial function, bioenergetics) also improves with aerobic exercise during weight loss (15).

Body Awareness.

While losing weight comes with many positive benefits, it is not abnormal for patients to report a lack of body awareness. Our data includes patients reporting feeling uncoordinated or “disconnected” from their bodies after losing large amounts of weight. Exercise professionals are well-positioned to assist with improving balance, core strength, mobility, agility, and flexibility using various modalities to target the body-mind connection.

Progressing with Care.

Now that there is an opportunity to program based on the relevant and personal needs of clients taking AOMs, it remains more important than ever to be mindful of appropriate progressions, regressions, and specific considerations for persons carrying excess body weight when exercising. Strategies include using shorter bouts of activity, accumulating activity minutes across the week, and starting low and progressing intensity slowly. These strategies have been shown to be effective in weight loss interventions that have included aerobic, resistance, and yoga exercise (7,16,17).

Medication Changes.

It is important for exercise professionals to remain aware of changes in AOM doses. The timeline for increasing the dose of AOMs is highly variable and is determined by the provider based on what is clinically appropriate and tolerated by the patient. A change or increase in dose can result in an increase in side-effects. This may impact exercise adherence and any planned progression in the exercise program. There is little evidence currently to understand how AOMs may impact exercise performance in general or on the days that injections are administered. Exercise professionals should encourage regular dialogue around how their clients feel before, during, and after exercise, and be aware of dose changes and individual side-effect patterns experienced across the week.

Engagement and Adherence Considerations:

Stigma.

When interviewing patients on AOMs, many reported feeling judged by exercise professionals for “taking the easy way out,” or for not having enough willpower to be successful with diet and/or exercise alone. Exercise professionals should pay special attention to avoid developing weight-related biases and promoting stigmatic behavior (18) when talking to clients and in online and social media communications. Recognizing that obesity is a disease and developing programming that supports patients on these medications can build trust and promote long-term engagement in physical activity.

Self-efficacy.

Self-efficacy for exercise can be impacted by many factors including previous experiences with activity and what they expect to get out of participating (outcome expectancies, value) (19). Previous experiences can shape a client’s perspective around exercise. Our data has taught us the following:

• Many patients on these medications have exercised for weight loss before and they may not be new to physical activity, so it should not be assumed that they do not know how to exercise.

• Some patients previously reported having negative experiences exercising.

• Patients report failing to maintain weight loss with exercise previously, so they question the impact exercise might have on their current weight loss journey.

Exercise professionals can help reshape how clients taking an AOM value exercise by programming for personal health benefits rather than burning more calories.

Discomfort and Affect.

Many patients in our survey reported feeling both physically and mentally uncomfortable during exercise. This includes feeling physically unable to tolerate the dose of exercise, experiencing musculoskeletal pain beyond moderate discomfort that kept them from wanting to return to workouts, and being verbally pushed (negatively) to work through a program. Affect, or how an individual feels during a single exercise session is predictive of long-term exercise behavior, and negative affective responses are typically associated with exercise avoidance (20). Additionally, patients expressed to us that they have experienced feeling uncomfortable with the way they look during exercise and have concern over being judged by others while exercising. It remains important for exercise professionals and facilities to create welcoming environments where clients with obesity feel comfortable and physically and mentally supported while exercising.

Summary

As we enter this exciting new era, there is still a lot to learn. However, the considerations presented provide a starting point for exercise professionals to tailor prescriptions and environments in a relevant way for patients taking AOMs. As exercise professionals contribute to the holistic care of persons with obesity, they must remain informed of the unique biological, behavioral, and environmental contributors that may be impacting their clients’ body weight, stay current with AOMs, and develop a comprehensive referral network for when their clients require support (dietary, psychiatric, medical) beyond exercise professionals’ scope of practice.

While this serves as a guide providing considerations in this new landscape, obesity care from the exercise perspective should not be oversimplified into a single method and should always require a personalized evaluation for each client.

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Apply It!

This article will inform and help readers:

• Gain an understanding of how contemporary anti-obesity medications work and how they are indicated, prescribed, and managed for the treatment of obesity.

• Reframe exercise prescriptions for clients taking an anti-obesity medication to focus on health and well-being, rather than on caloric expenditure to further enhance weight loss.

• Recognize key targets for developing exercise programs based on the current state of the research and perspectives from clients taking anti-obesity medications.

Bridging the Gap

As anti-obesity medications (AOMs) have increased in use, this has been concurrent with increased media attention, and there is also an enhanced focus on how lifestyle factors may fit within these treatments. It is important for exercise professionals to follow the research and remain aware of the effectiveness of AOMs currently approved and those in the development pipeline. This includes understanding indications for the use of AOMs, and how they are managed to contribute to the holistic care of clients. These highly effective agents are considered “life-changers” for patients with chronic obesity, and there is an opportunity for exercise professionals to reframe programming targets and focus on the health, well-being, and relevant exercise-related needs of their clients.

Pulled Text.

1. It is important for exercise professionals to have a deeper understanding of the effectiveness and indications of contemporary anti-obesity medications (AOMs), along with the opportunities that these present for patients with obesity and the exercise industry.

2. Most board-certified obesity clinicians who prescribe AOMs may refer to these as being an additional tool in the obesity management toolbox. This is because AOMs only impact how much you eat, not how well. Moreover, AOMs are not causing patients to move more.

3. Currently, there is limited research to understand how physical activity impacts the effectiveness of AOMs. Yet, there is an abundance of evidence supporting the independent effects of exercise on health even when an individual has obesity. However, this may require exercise professionals to reposition physical activity to the patient as an important adjunct to their obesity care.

Recommended Readings:

• A Perspective on Anti-Obesity Medications (ACSM Blog): https://www.acsm.org/blog-detail/acsm-bulletin-blog/2023/10/24/a-perspective-on-anti-obesity-medications?utm_source=Informz&utm_medium=Email&utm_campaign=Informz_Bulletin23_10-26&_zs=f6ItW&_zl=lAUo3

• Navigating the Impact of New Weight Loss Medications (ACSM Blog): https://www.acsm.org/home/featured-blogs---homepage/acsm-blog/2023/12/18/navigating-the-impact-of-new-weight-loss-medications

• The Role of Lifestyle Modification with Second-Generation Anti-Obesity Medications: Comparisons, Questions, and Clinical Opportunities (Open Access Review Article): https://link.springer.com/article/10.1007/s13679-023-00534-z#citeas

• Contemporary Treatments for Obesity: Physical Activity in the Context of Anti-Obesity Medications (Journal Article – TJACSM): In Review

Biography

Renee J. Rogers, PhD, FACSM, is a Senior Scientist at the University of Kansas Medical Center in the Department of Internal Medicine, Division of Physical Activity and Weight Management. Dr. Rogers Chairs both ACSM’s Strategic Health Initiative (SHI) for Behavior Change and International Health & Fitness Summit committees. She focuses her work on the unique intersection between biology/physiology and behavior to design and implement weight management interventions that emphasizes physical activity engagement and adoption.