GLP-1 medications are changing obesity treatment. But are we getting their full value?
GLP-1 medications represent one of the most important advances in cardiometabolic medicine in decades. They produce substantial weight loss, improve metabolic health, and reduce cardiovascular events in certain high-risk populations.
The evidence supporting these medications is compelling.
But there is an important question that receives considerably less attention.
How much additional health benefit might patients be missing when GLP-1 medications are prescribed without a structured exercise plan?
A patient can lose 30 or 40 pounds while remaining sedentary. Their blood pressure and metabolic risk factors may improve, yet their muscular strength, exercise capacity, and physical function may remain largely unchanged.
The medication may be working exactly as intended. But has the patient achieved the full health benefit that might otherwise have been possible?
And if exercise offers additional benefits, why is it so often treated as an optional recommendation rather than an integral component of medical weight-loss treatment?
Do GLP-1 medications protect the heart without exercise?
In the landmark SELECT trial, published in the New England Journal of Medicine, semaglutide reduced major cardiovascular events by 20% among more than 17,000 adults with established cardiovascular disease and overweight or obesity, but without diabetes.¹
That is a substantial clinical benefit.
However, SELECT raises another important question. Would the magnitude of cardiovascular protection have been different if participants had also followed a structured exercise program?
Participants received standard cardiovascular care, including lifestyle advice, but exercise itself was not randomized or systematically evaluated as a modifier of treatment benefit.
Consequently, we do not know, at the time of this writing, whether semaglutide's cardiovascular treatment effect differs between individuals who are sedentary and those who exercise regularly.
This distinction matters.
There is no evidence that exercise is required for semaglutide to provide cardiovascular protection. Equally, there is insufficient evidence to conclude that medication alone achieves the same overall health benefits as medication combined with regular exercise.
A 2026 study published in The Lancet Diabetes & Endocrinology examined more than 98,000 U.S. veterans with type 2 diabetes. Investigators found that GLP-1 medication use combined with favourable lifestyle behaviours was associated with lower cardiovascular event risk than either approach considered separately.²
Physical activity was one of eight lifestyle behaviours assessed. As an observational study, these findings cannot establish whether exercise specifically increases the cardiovascular efficacy of GLP-1 medications.
Nevertheless, they reinforce the possibility that pharmacotherapy and healthy lifestyle behaviours may provide complementary benefits.
The question is no longer simply whether GLP-1 medications work.
It is whether we are organizing care in a way that allows patients to realize the greatest possible health benefit.
Weight loss is not the same as improved fitness or strength
A second concern relates to the quality of weight loss.
Substantial weight reduction, whether achieved through medication or other means, often involves reductions in both fat and lean body mass.
Lean mass includes skeletal muscle, water, organs, and other non-fat tissues. Accordingly, lean-mass loss does not necessarily represent an equivalent loss of functional muscle. Nevertheless, preserving muscular strength and physical function is particularly important during weight reduction, especially among older adults.
A 2025 multidisciplinary advisory published in the American Journal of Clinical Nutrition emphasized adequate nutrition, resistance training, and monitoring muscle strength and function during GLP-1 treatment.³
This distinction was also explored during a recent My Heart Fitness conversation with Dr. Mirey Karavetian, a nutrition scientist from MYLA Health.
Consider someone who loses 40 pounds while taking a GLP-1 medication.
Their weight is lower, and several cardiovascular risk factors may have improved.
But are they stronger? Can they climb stairs more comfortably? Have they improved their endurance? Are they more physically capable?
These questions reflect an important distinction between losing weight and improving the quality of one's health.
Aerobic exercise and resistance training contribute different, complementary benefits.
Aerobic activity improves cardiovascular endurance and cardiorespiratory fitness. Resistance training helps preserve muscular strength and functional capacity. Adequate protein intake supports muscle maintenance, but does not replace resistance exercise.
Weight loss should therefore be evaluated alongside changes in strength, fitness, and physical function, rather than assuming that improvement in one necessarily produces improvement in the others.
Does combining GLP-1 medications with exercise produce better results?
Randomized clinical trials provide encouraging evidence.
In a trial published in the New England Journal of Medicine, Lundgren and colleagues compared structured exercise, liraglutide, their combination, and placebo following an initial period of dietary weight loss.⁴
The combined intervention improved healthy weight-loss maintenance more than either treatment alone.
A subsequent analysis published in Sports Medicine in 2026 found that combining exercise with liraglutide produced greater improvements in cardiorespiratory fitness and stair-climbing performance than liraglutide alone.⁵
A further follow-up suggested that incorporating exercise also improved the maintenance of weight loss after treatment ended.⁶
These trials did not establish additional reductions in heart attacks or strokes, and they did not determine whether exercise should begin before medication.
However, they demonstrate something clinically important.
The benefits of treatment should not be judged exclusively by the amount of weight lost.
Structured exercise can provide improvements in fitness and physical function that medication alone may not deliver.
Should exercise begin before GLP-1 treatment?
There is a reasonable argument for establishing exercise habits before starting GLP-1 medications, whenever clinically appropriate.
For patients seeking treatment primarily for weight loss, developing a manageable routine of aerobic and resistance exercise before medication begins may provide an important behavioural foundation.
Patients would already have begun addressing barriers to physical activity, developing confidence, and establishing habits before adapting to medication-associated changes in appetite and body weight.
This does not mean exercise should become a prerequisite for receiving treatment.
Patients with established cardiovascular disease, type 2 diabetes, or other compelling indications may benefit from GLP-1 therapy regardless of their current physical activity. Some individuals also have physical limitations for which weight loss may make exercise more achievable.
Medication should not be unnecessarily delayed.
But whether exercise begins before medication or alongside it, an important principle remains.
Exercise should be incorporated into the treatment plan from the outset, rather than introduced only after weight loss has begun.
If exercise matters, who is responsible for making it happen?
In my recent editorial in the Journal of the American College of Cardiology, “From Insight to Infrastructure: Managing Cardiorespiratory Fitness,” I tried to stress that the problem is not a lack of evidence demonstrating the importance of exercise.⁸
It is our limited ability to translate that evidence into routine clinical practice.
Healthcare has developed sophisticated mechanisms for prescribing medications, monitoring their effects, and adjusting treatment according to clinical response.
Yet exercise is frequently recommended without a corresponding prescription, structured support, or longitudinal measurement.
The contrast becomes particularly striking with GLP-1 medications.
Consider the resources being committed to pharmacological weight management. The medication is prescribed, reimbursed where coverage is available, and monitored for efficacy and adverse effects.
But what happens to the exercise recommendation?
Is physical activity assessed at baseline? Is resistance training incorporated? Is there a mechanism for monitoring changes in fitness and functional capacity?
And perhaps most importantly, who is responsible for ensuring that exercise becomes part of the patient's ongoing care?
These questions extend beyond individual patients.
For clinicians, the absence of a structured exercise pathway limits the ability to support and evaluate an important component of self-management.
For patients, it may mean missing opportunities to improve strength, mobility, fitness, and independence.
And for the organizations paying for treatment, it raises a legitimate question about whether the full potential value of an increasingly important healthcare investment is being realized.
This does not imply that access to medication should depend on achieving an exercise target. Such a requirement could disadvantage patients with significant medical or functional limitations.
It does, however, raise a different question.
If healthcare systems are prepared to invest in GLP-1 medications, should they not also ensure that patients have meaningful access to the exercise support that belongs alongside treatment?
Beyond weight loss: what should define successful treatment?
Cardiorespiratory fitness is among the strongest predictors of long-term health outcomes. In a study involving more than 750,000 U.S. veterans, individuals in the lowest fitness category had approximately four times the mortality risk of those in the highest fitness category, after adjustment for other risk factors.⁷
Although observational, these findings reinforce the importance of fitness as a clinical measure.
Exercise exposure can be quantified through intensity, duration, and accumulated weekly MET-minutes. Muscular strength and physical function can also be monitored over time.
Together, these measures provide information that body weight alone cannot capture.
For patients receiving GLP-1 medications, a more complete approach to treatment would therefore consider weight reduction alongside meaningful improvements in aerobic activity, resistance exercise, fitness, and function.
This is the broader clinical challenge being addressed through My Heart Fitness: making exercise a measurable, supported, and clinically meaningful part of cardiovascular prevention.
Are we missing an opportunity?
GLP-1 medications have fundamentally changed the treatment of obesity and cardiometabolic disease.
Their benefits should not be understated.
But neither should their success distract from the importance of exercise, muscular strength, and physical fitness.
The evidence suggests that medication and structured exercise can provide complementary benefits. What remains less certain is how best to integrate these interventions, and whether doing so more consistently can improve long-term cardiovascular outcomes.
Perhaps the most important question is not whether GLP-1 medications should be prescribed before or after someone begins exercising.
It is why exercise remains so poorly integrated into a treatment strategy in which its importance is already widely acknowledged.
If the objective is better health rather than weight loss alone, that is a question clinicians, patients, and healthcare payers should increasingly be asking.
Frequently Asked Questions
Do I still need to exercise on a GLP-1?
Yes. GLP-1 medications provide important benefits, but aerobic exercise and resistance training offer additional benefits for cardiovascular fitness, muscular strength, and physical function.
Should I start exercising before taking semaglutide?
When medically appropriate, establishing an achievable exercise routine before treatment may help develop sustainable habits. However, exercise is not a prerequisite for receiving semaglutide, and medication should not be delayed when clinically indicated.
Do GLP-1 medications reduce cardiovascular risk without exercise?
Semaglutide has demonstrated cardiovascular event reduction in defined high-risk populations. Whether the magnitude of this benefit differs according to exercise participation or baseline fitness remains uncertain.
Why is strength training important during GLP-1 treatment?
Substantial weight loss can involve reductions in lean body mass. Resistance training, together with adequate nutrition, helps support muscular strength and function during weight reduction.
References
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389:2221–2232. doi:10.1056/NEJMoa2307563
Nguyen XMT, Li Y, Czernichow S, et al. Combined associations of GLP-1 receptor agonists and a healthy lifestyle with cardiovascular outcomes among individuals with type 2 diabetes: a prospective cohort study. Lancet Diabetes Endocrinol. 2026;14:317–326. doi:10.1016/S2213-8587(25)00395-X
Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint advisory. Am J Clin Nutr. 2025;122:344–367. doi:10.1016/j.ajcnut.2025.04.023
Lundgren JR, Janus C, Jensen SBK, et al. Healthy weight loss maintenance with exercise, liraglutide, or both combined. N Engl J Med. 2021;384:1719–1730. doi:10.1056/NEJMoa2028198
Jensen SBK, Fiorenza M, Juhl CR, et al. Physical fitness with exercise and GLP-1 receptor agonist treatment alone or combined after diet-induced weight loss. Sports Med. 2026;56:1785–1800. doi:10.1007/s40279-025-02386-0
Jensen SBK, Blond MB, Sandsdal RM, et al. Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment. eClinicalMedicine. 2024;69:102475. doi:10.1016/j.eclinm.2024.102475
Kokkinos P, Faselis C, Samuel IBH, et al. Cardiorespiratory fitness and mortality risk across the spectra of age, race, and sex. J Am Coll Cardiol. 2022;80:598–609. doi:10.1016/j.jacc.2022.05.031
Alter DA. From insight to infrastructure: managing cardiorespiratory fitness. J Am Coll Cardiol. 2026;88:279–281. doi:10.1016/j.jacc.2026.03.053