Obesity is recognized as a major global health challenge, with the World Health Organisation (WHO) declaring it a global epidemic.
To help manage obesity, there is a growing demand for weight-loss drugs, including GLP-1s such as Wegovy, Zepbound, and Foundayo, which all have Food and Drug Administration (FDA) approval for this indication.
According to a nationally representative United States survey by the Kaiser Family Foundation (KFF), about one in eight adults, or 12%, say they have ever taken a GLP-1 drug.
Among adults who have been told by a doctor that they have overweight or obesity, this proportion increases to roughly one in five, or 22%.
Despite obesity medications helping people to achieve clinically meaningful weight loss when used in conjunction with lifestyle changes, new research suggests these benefits may not translate into meaningful improvements in quality of life or cardiovascular health for many patients.
The analysis, published in The BMJ, found that while several obesity drugs were associated with significant weight reduction, only a small number showed evidence of improving heart-related outcomes after 1 year of treatment.
These findings highlight the importance of tailoring obesity treatment decisions to each individual, taking into account expected benefits, potential harms, treatment burden, costs, availability, and personal preferences.
To better understand how obesity drugs compare, researchers reviewed evidence from randomized controlled trials assessing the medications against lifestyle interventions, placebo, or other drugs.
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The review included 262 trials involving 99,791 participants, with a median age of 49 years and a median body mass index (BMI) of 35. Around 63% of the participants were female.
The studies examined 19 currently available and emerging obesity medications, with follow-up periods ranging from 12 to 172 weeks.
Researchers assessed several outcomes, including weight loss, changes in body fat and muscle mass, quality of life, gastrointestinal side effects, fatigue, gallbladder-related problems, and cardiovascular outcomes
Although the trials varied in quality, researchers used the established GRADE system to assess how reliable the evidence was.
While it is established that obesity drugs can help lead to substantial weight loss, the benefits can vary widely. The greatest weight reductions after 1 year, compared with lifestyle changes alone, were seen with:
Several newer medications, including retatrutide, ecnoglutide, and mazdutide, also appeared to produce substantial weight loss. However, researchers noted that evidence for these treatments remains limited and is considered low or very low certainty.
The study also found a consistent pattern: Greater weight loss was often linked to a higher risk of side effects and of people stopping treatment.
The researchers found that obesity medications producing larger reductions in body weight were also more likely to cause unwanted effects, particularly gastrointestinal symptoms such as nausea and digestive problems.
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Loss of lean mass, which includes muscle tissue, was another concern. For example, tirzepatide produced the largest reduction in fat mass, decreasing fat by 25.7%. However, it was also associated with the largest reduction in lean mass, at 8.3%.
The researchers note that this demonstrates a trade-off between the benefits of weight reduction and potential harms associated with treatment.
“Obesity drugs should not be judged by weight loss alone,” emphasized study author Sheyu Li, PhD, a clinical professor and endocrinologist in the Department of Endocrinology and Metabolism, and evidence-based medicine methodologist in MAGIC China Centre, West China Hospital of Sichuan University.
“The decision should be based on individualised benefits and harms, including cardiovascular prevention in those at high risks, fat mass loss, lean mass loss, fatigue and other drug-related discomfort,” said Li.
Despite the effectiveness of some obesity medications for weight loss, most did not show clear improvements in quality of life.
The researchers found that no obesity drug convincingly reduced the risk of kidney failure or produced clinically meaningful improvements in patients’ reported quality of life.
Among the drugs studied, only injectable semaglutide was associated with a lower risk of several major cardiovascular outcomes, including a 19% reduction in risk of death from any cause, a 28% reduction in heart attack risk, and a 57% reduction in heart failure risk.
Tirzepatide was also linked with a reduced risk of heart failure, lowering risk by 51%.
“The quality of life assessment is an overall measure, including all aspects of daily life,” Li explained to Medical News Today.
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“The no improvement conclusion is based on an average effect. In adults with higher cardiovascular benefits, drugs such as semaglutide and tirzepatide provide promising cardiovascular benefits, and I do believe the overall quality of life is different in those with and without incident cardiovascular diseases,” he told us.
“In trade off, many people experience fatigue and gastrointestinal and other discomfort when using the drugs. Nevertheless, in the study population, only a small proportion of the population are at higher risk of cardiovascular risk, and the average effect on quality of life may be neutralised by lower risk people,” Li added.
“It also means that those solely ‘benefit’ from weight loss without any meaningful event rate reduction does not necessarily mean a meaningful improvement of quality of life,” he noted.
“Not all people living with obesity need drugs. A concept of readiness is relevant here in practice. To be noted, body weight is only a number and a surrogate outcome that needs validation in more patient relevant events. During the decision making in using or not using obesity drugs, patient important outcomes are more relevant than the number of body weight reduction.”
– Sheyu Li, PhD
Mir Ali, MD, bariatric surgeon, bariatric medicine specialist and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, who was not involved in the study, shared a similar sentiment with MNT.
“While many of these medications provide excellent weight loss, the key takeaway is that long-term weight control remains a complex and difficult challenge,” said Ali.
He pointed out that: “Quality of life is highly subjective and multifactorial. While weight loss is generally very beneficial, it may not necessarily improve all health conditions or aspects of a patient’s life simultaneously. I explain to my patients that these medications are tools to help facilitate changes in eating and lifestyle habits. The best results are achieved when patients are able to implement meaningful, long-term lifestyle changes.”
The study authors also note that many of the included studies had relatively short follow-up periods, making it difficult to determine the long-term effects of obesity medications on safety, quality of life, and heart and kidney health.
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They also highlight that evidence for some newer treatments remains limited, and participants in the clinical trials may not fully represent the wider population using these medications in everyday healthcare settings.
These findings provide an updated comparison of available and emerging obesity treatments, which may help healthcare professionals and patients discuss the potential advantages and disadvantages of different options.
The researchers conclude that obesity treatment decisions should be personalized, balancing likely benefits with possible harms, costs, access, and patient preferences.
“Benefits vary across persons based on their own individualised health priority,” Li highlighted. “The burdens or complications due to obesity determine the clinical relevance of obesity, and of course the burden includes the expectation of future health.”
“Clinicians and patients may consider shared decision making by discussing the expected weight loss alongside evidence for cardiovascular benefit, side effects, uncertainty, treatment burden, cost, and the long-term use. The discussion should focus on what matters most to the patient and support a shared decision, rather than presenting one medicine as universally ‘best’,” he added.
In a linked editorial, researchers say the review provides valuable information for discussions between patients and clinicians as the number of available obesity medications continues to grow.
They also add that future studies focusing on individual patient characteristics and longer-term outcomes, including survival, will be important for improving treatment decisions.
“Treatment goals should extend beyond weight to include general wellbeing including physical function, quality of life, muscle strength, tolerability, and prevention of obesity-related complications,” Li told MNT. “As stated, quality of life was determined by the painful burden due to obesity and its improvement by its benefits from weight loss.”
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“People with lower muscular volume at baseline should take more attention to muscular preservation during the drug use. Those at higher cardiovascular risks may take more benefits from cardiovascular prevention,” he advised.
“Weight loss is only one component of overall health. The best approach is to fully inform patients on how these medications work, including the potential risks and benefits,” Ali further noted.
“It is also vital to set realistic goals to prevent frustration and to ensure patients understand that these medications typically require long-term use. Also, a regular exercise regimen — even walking — can help preserve muscle and facilitate weight loss,” the physician suggested.
“Patients should consider their own individualised health goals, risk of obesity-related complications, expected benefits beyond weight loss, possible side effects, convenience, cost, access, and willingness to continue treatment long term,” said Li.
“There is no single best medicine for everyone; the right choice depends on each patient’s risks, priorities, and preferences,” he pointed out.
And according to Ali, “patients must consider their readiness to make significant, long-term lifestyle changes while using the medication as an aid.”
“Additionally, practical factors such as insurance coverage, cost, and the necessity of long-term use are essential considerations before starting treatment,” he concluded.
