IPM Take
The GLP-1 era is exposing a political imbalance in cardiometabolic care. Health systems can price, prescribe and reimburse medicines, but they still struggle to fund exercise programmes, supervised lifestyle support, active environments and long-term maintenance pathways. New Nature Metabolism findings do not weaken the case for GLP-1 medicines. They weaken the fantasy that medicines alone can replace prevention infrastructure. Personalised cardiometabolic care should combine pharmacology with structured movement, not turn exercise into an unpaid footnote.
Executive Summary
A Nature Metabolism News & Views article published highlighting new findings from Sandsdal, Holt and colleagues on exercise, liraglutide and vascular health during weight-loss maintenance. In a prespecified secondary analysis of the S-LiTE trial, 130 adults with obesity who completed diet-induced weight loss were randomised to placebo, exercise, liraglutide or exercise plus liraglutide for 52 weeks.
The study found that exercise alone, and exercise combined with liraglutide, reduced carotid intima-media thickness and lowered selected pro-inflammatory cytokines. Combination treatment also improved endothelial function biomarkers. Liraglutide alone maintained weight loss, but did not show the same vascular and inflammatory improvements observed with exercise-containing interventions.
This is not a verdict against GLP-1 receptor agonists. Larger outcome trials, including SELECT, have shown cardiovascular benefits with semaglutide in adults with overweight or obesity and established cardiovascular disease. But the S-LiTE analysis raises an important implementation question: if exercise has cardiovascular effects beyond weight loss, why do health systems still treat it as advice rather than reimbursable care?
Globally, WHO estimates that 31% of adults, around 1.8 billion people, did not meet recommended physical activity levels in 2022. If obesity treatment becomes pharmacological without serious investment in physical activity systems, cardiometabolic prevention will remain partial, expensive and unequal.
Why it matters
- Policymakers and public authorities: Obesity and cardiovascular strategies need to fund physical activity infrastructure, not just treatment access. Exercise should be built into care pathways, transport policy, schools, workplaces and community health systems.
- HTA bodies and payers: Assessment of obesity medicines should consider whether outcomes improve when pharmacotherapy is paired with structured lifestyle and exercise support. Reimbursement models should not pay for drugs while ignoring the service model around them.
- Clinicians and providers: Exercise should not be reduced to generic advice. Patients need structured, realistic, culturally appropriate and medically safe programmes, especially after weight loss or when starting anti-obesity medicines.
- Patients and advocates: The message should not be blame. Many people cannot exercise safely or regularly because of cost, disability, work schedules, neighbourhood safety, caregiving responsibilities or lack of supervised support.
- Industry / innovation partners: The future market will not be won by weight-loss percentages alone. Cardiometabolic value will depend on long-term risk reduction, maintenance, adherence and integration with broader prevention pathways.
The GLP-1 boom has changed obesity care. It has also created a policy illusion.
The illusion is that pharmacology can do the work of prevention infrastructure.
A new Nature Metabolism News & Views article, discussing findings from Sandsdal, Holt and colleagues, cuts through that story. In a prespecified secondary analysis of the S-LiTE trial, adults with obesity first completed an eight-week low-calorie diet and lost an average of 13.7 kg. They were then randomised for 52 weeks to placebo, exercise, liraglutide, or exercise combined with liraglutide.
The results matter because they separate weight maintenance from vascular health.
Liraglutide helped maintain weight loss. That is clinically relevant. But exercise alone, and exercise combined with liraglutide, reduced carotid intima-media thickness, a surrogate marker of vascular health, and lowered selected inflammatory markers. Combination treatment also improved endothelial function biomarkers. Liraglutide alone did not show those same improvements.
This is not an anti-GLP-1 story.
GLP-1 receptor agonists have become central to the new cardiometabolic landscape for good reasons. Semaglutide reduced major adverse cardiovascular events by 20% in the SELECT trial among adults with overweight or obesity and established cardiovascular disease but without diabetes. These medicines are not just cosmetic weight-loss tools. They are becoming cardiovascular prevention tools.
But the Nature Metabolism findings make one thing harder to ignore: weight loss is not the whole pathway to vascular protection.
Exercise affects inflammation, endothelial function, cardiorespiratory fitness, muscle metabolism, insulin sensitivity, blood pressure, mood and functional capacity. Some of these benefits may not be replicated by medication alone. If health systems treat exercise as optional lifestyle advice while treating drugs as the serious intervention, they are building an incomplete cardiometabolic model.
That model will be expensive. It will also be unequal.
Globally, WHO estimates that nearly one third of adults, around 1.8 billion people, did not meet recommended physical activity levels in 2022. The world is off track for the 2030 target to reduce physical inactivity. Physical inactivity increases risk of cardiovascular disease, type 2 diabetes, dementia and several cancers. It is not a soft behavioural issue. It is a structural determinant of noncommunicable disease.
The barriers are not evenly distributed. Women, older adults, people in unsafe neighbourhoods, people with disabilities, people working long or insecure hours, and communities without parks, pavements, cycling routes or affordable exercise facilities are all less likely to benefit from “just move more” advice. A prescription for exercise is meaningless if the patient has nowhere safe, affordable or realistic to do it.
That is the policy failure hiding inside the obesity drug revolution.
Health systems are learning how to reimburse high-cost medicines, negotiate supply and define eligibility thresholds. But many still do not know how to commission supervised exercise, long-term behavioural support, community-based maintenance programmes, active transport infrastructure or rehabilitation-style cardiometabolic services.
The result is a two-tier prevention system. Medicines become formal care. Exercise remains personal responsibility.
That is backwards.
If exercise improves vascular health during weight-loss maintenance, then exercise support should be treated as a clinical service, not a motivational slogan. That means referral pathways, trained staff, reimbursement, monitoring, adaptation for comorbidities and digital support where appropriate. It also means recognising that different patients need different models: supervised exercise for high-risk patients, community programmes for others, home-based options, hybrid support, workplace interventions, and integration with obesity, diabetes and cardiac rehabilitation pathways.
There are also implications for HTA and payer policy.
Anti-obesity medicines are increasingly assessed through weight loss, cardiometabolic markers and, where available, cardiovascular outcomes. But if the best outcomes require structured exercise support, then payers should not evaluate the drug in isolation from the pathway. The question should be: what combination of medicine, exercise, nutrition, monitoring and follow-up produces durable risk reduction?
That is especially important as newer, more potent incretin therapies expand demand. Without a pathway, patients may lose weight on treatment, regain after discontinuation, or miss the vascular and functional gains that exercise can provide. The S-LiTE trial’s longer-term follow-up also suggests that exercise-containing groups had better maintenance of body weight and body composition one year after supervised exercise ended, while weight gain was observed after stopping liraglutide alone.
There is a blunt lesson here for personalised medicine.
Personalised care is not only choosing the right drug. It is choosing the right combination of interventions for the right person, in the right system. For some patients, GLP-1 therapy may be essential. For others, structured exercise and diet support may be enough. For many, the best pathway will be combined.
But combination care requires system design.
It requires payers to reimburse more than molecules. It requires clinicians to have places to refer patients. It requires cities to make physical activity possible. It requires employers and schools to stop treating movement as an afterthought. It requires governments to recognise that the built environment is cardiometabolic policy.
The GLP-1 boom should not become an excuse to neglect exercise. It should be the moment when health systems finally admit that lifestyle advice without infrastructure is not prevention.
Medicines can help reduce risk. Exercise can help change the biology of that risk. Policy has to make both accessible.
Otherwise, cardiometabolic care will become very good at prescribing weight loss, and still too weak at building health.
