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A review published in The BMJ looks at obesity drugs and quality of life and heart health.
Dr Hamid Merchant, Head of Department for Biosciences at the University of East London, said:
“The press release broadly reflects the findings of the BMJ analysis, but the headline risks oversimplifying a complex picture, and can be seen by many as misleading. The study itself confirms that several modern obesity medicines, including semaglutide and tirzepatide, can achieve substantial and clinically meaningful weight loss. While improvements in quality of life did not exceed the authors’ predefined threshold for a clinically important difference, this should not be interpreted as evidence that patients derive no benefit. Importantly, injectable semaglutide was associated with reductions in all-cause mortality, myocardial infarction and heart failure, while tirzepatide was associated with reduced heart failure risk. The findings reinforce the need for personalised treatment decisions that balance benefits, risks, treatment burden and patient preferences, alongside ongoing lifestyle interventions.
“The findings regarding quality of life require particularly careful interpretation. The study did notconclude that these medicines fail to improve quality of life. Rather, improvements observed with drugs such as semaglutide and tirzepatide did not exceed the authors’ predefined threshold for a clinically important difference on a generic quality-of-life scale. The selected threshold of 10 points on the SF-36 scale is based on published methodology but remains, to some extent, a judgement-based criterion. Alternative thresholds have been proposed in the literature and may have led to different interpretations of the data. Therefore, these findings should not be interpreted as evidence that patients experience no meaningful day-to-day benefits from treatment.
“There is a risk that readers could conclude that these medicines are ineffective because they do not improve ‘quality of life or heart health’. That would be an inaccurate interpretation of the underlying evidence. The study demonstrated average weight reductions approaching 10-15% with some treatments, which are clinically meaningful and can positively influence glycaemic control, sleep apnoea, mobility, osteoarthritis symptoms, metabolic dysfunction-associated steatotic liver disease, and future cardiometabolic risk. These broader health benefits are not sufficiently emphasised in the headline.
“The cardiovascular messaging also requires nuance. The meta-analysis does find that subcutaneous semaglutide reduced all-cause mortality and myocardial infarction, while both semaglutide and tirzepatide reduced heart failure risk. However, much of the cardiovascular evidence derives from large outcome trials conducted in higher-risk populations, and the authors acknowledge that many obesity trials remain relatively short and were not primarily designed to evaluate cardiovascular outcomes. Therefore, the statement that few drugs show cardiovascular benefit is technically correct, but it should not be interpreted as evidence that semaglutide or tirzepatide lack cardiovascular benefits.
“Overall, the headline ‘Most obesity drugs do not improve quality of life or heart health‘ is likely to be interpreted by many readers as meaning ‘these drugs do not work’. That is NOT what the study found. A more accurate interpretation would be that while obesity medicines vary in their benefits and harms, several produce substantial weight loss, some demonstrate important cardiovascular benefits, and the quality-of-life findings depend heavily on how clinically meaningful improvement is defined.”
Dr Sonya Babu-Narayan, Clinical Director at the British Heart Foundation and consultant cardiologist, said:
“This type of analysis enables researchers to create a large pool of data by combining multiple studies, but the findings are limited by the consistency of the data included and inability to drill down to individual patient characteristics. For some of the medicines included in the analysis, the evidence is still emerging with trials in progress, so it is too early to make strong conclusions of their relative effects.
“We already know, from randomised controlled trials which give us robust evidence, that these medicines have a role beyond being an ‘obesity drug’ and helping with weight loss alone. Large trials of semaglutide have found fewer heart attack and stroke several years down the line among those living with both cardiovascular disease and overweight or obesity. It is important that these medicines are therefore available to the cardiovascular patients who may benefit from them. The findings reinforce that GLP-1 medicines, prescribed by a doctor, are an important option for some people and that they work best alongside healthy eating, regular physical activity including strength exercises and other healthy behaviours.”
Dr Marie Spreckley, Weight Management Researcher, University of Cambridge, said:
“This is a comprehensive and well-conducted systematic review and network meta-analysis that provides an important comparative overview of the rapidly evolving evidence on obesity medications. A key strength is that the authors looked beyond weight loss alone and assessed outcomes that matter to patients and healthcare systems, including quality of life, cardiovascular outcomes, body composition and potential harms.
“The conclusions are broadly supported by the data, but need to be interpreted carefully. The findings do not show that obesity medications have no wider health benefits. Rather, they highlight that while the evidence for weight loss is strong, evidence for some longer-term outcomes is still developing and differs considerably between individual medications.
“This is particularly important for cardiovascular outcomes. Many weight-loss trials were not primarily designed or sufficiently long to assess outcomes such as heart attacks, heart failure or mortality. The absence of demonstrated benefit for all medications should therefore not be interpreted as evidence that these benefits do not exist. Importantly, this review did identify cardiovascular benefits for some treatments and patient groups.
“The quality-of-life findings are also important. The authors found that, on average, medications did not improve quality-of-life scores in trials beyond established thresholds considered clinically meaningful. However, quality of life is complex and varies between individuals. While standardised measures provide valuable information, they may not capture all aspects of treatment experience that matter to people living with obesity.
“The review also highlights the importance of balancing benefits and potential harms. Side effects, particularly gastrointestinal symptoms, were more common with several treatments, and changes in body composition highlight the importance of supporting overall health outcomes during treatment.
“Overall, this study reinforces the importance of moving beyond weight loss as the only measure of success. Obesity is a complex chronic condition, and treatment decisions should consider benefits, potential harms, individual preferences and long-term health outcomes.”
Prof Liam Smeeth, Director of and Professor of Clinical Epidemiology at London School of Hygiene & Tropical Medicine (LSHTM), said:
“This rigorous systematic review of the evidence accrued to date is very welcome. The conclusions are appropriately drawn from the data, and the results are credible because the contributing studies are well conducted randomised trial comparisons with low risk of bias.
“The results confirm that the GLP-1 agonist and related newer drugs do produce substantial weight loss that is maintained provided people remain on treatment. Troublesome side effects were more likely among those with higher levels of weight loss, consistent with more potent drugs having both higher adverse as well as beneficial effects.
“The benefits on improved quality of life were very small or non-existent. This was not because of a lack of evidence: quality of life data were measured in trials including more than 45,000 people. This poses an interesting challenge to the dominant narrative from social media, that losing weight is one – or even the main – major driver of human happiness.
“Evidence for beneficial effects on wider major health outcomes – such as cardiovascular disease and mortality – was found for subcutaneous semaglutide but was largely lacking for other drugs. It is possible such benefits may be seen for a wider range of drugs as more research data accrues, but this is by no means certain and should not be assumed.”
Prof John Wilding, Professor of Medicine, Department of Cardiovascular and Metabolic Medicine, University of Liverpool, said:
“Trying to analyse all these drugs (some are not approved for obesity, and unlikely to ever be approved for that indication), alongside older and newer approved treatments and others that are in various stages of clinical development in one article is a tall order and in my view creates a lot of inconsistencies and problems with interpretation.
“Some of them (metformin, SGLT2i, exenatide, dulaglutide) have never been approved for obesity treatment (they are treatments for diabetes) so it is not even clear why they have been included. Exenatide is no longer in use.
“Some drugs are not approved in many countries (e.g. Phentermine / Topiramate has never been approved in Europe or the UK) due to concerns over both efficacy and safety.
“Cagrisema is not yet approved anywhere in the world (the article states that it is).
“Including drugs in early development with only very short-term data, means that data is incomplete and there is no chance that long-term data will be available at this stage. This distorts overall interpretation.
“Some of the included trials are extremely short. 12 weeks is not enough time to make any meaningful analysis (it can be useful in very early-stage development as proof of concept), but any trial less than a year really should not be used to assess clinical benefit in my view.
“Loss of lean mass is included as a ‘harm’. It is a physiological consequence of weight loss (and is also seen in trials of diet and bariatric surgery) and in most cases it is not a harm, especially as those trials that have measured quality of life as an outcome show improvements in participant-reported measures of physical function. There may be a few individuals who develop sarcopenia but this is not really reported with sufficient frequency or accuracy to be able to be sure that this is a true adverse effect of treatment.
“The press release headline is not really correct as it implies there is evidence these drugs do not improve QoL or CV outcomes – what the article shows is lack of data for most of the included treatments, which is not the same as lack of effect. Tirzepatide already has data to show CV benefit in diabetes; trials in obesity are ongoing; there is also extensive evidence for liraglutide, SGLT2i, metformin, dulaglutide, oral semaglutide and subcutaneous semaglutide showing CV benefit in T2 diabetes. There is quite a lot of data showing the more modern, approved drugs do improve quality of life (this is clear from multiple published papers with semaglutide and tirzepatide, and also with some of the emerging data with cagrisema and retatrutide). The fact that effects are not sustained after stopping treatment is hardly surprising. We don’t expect that for other drugs used to treat chronic diseases like hypertension, dyslipidaemia, diabetes, asthma etc to continue to work if people stop taking them.”
Dr Adam Collins, Associate Professor of Nutrition, University of Surrey, said:
“This is a comprehensive review that covers a wide array of pharmaceutical interventions for the management of excess weight, including over 250 trials. It’s contemporary in that it includes drugs that are relatively new to practice. The authors present their findings by evaluating the certainty of the evidence and classifying drugs based on their benefits and adverse effects relative to typical lifestyle interventions. The study highlights GLP-1 receptor agonists as effective drugs for weight loss and body fat reduction (including both oral and injectable forms of semaglutide). Among these, the dual incretins Tirzepatide and CagriSema (cagrilinitide-semaglutide) lead to the greatest reductions. Yet in many cases, the benefits to quality of life and major health risks are not that clear. Plus, newer drugs to market, many in the US, currently lack sufficient certainty of evidence to judge them comparably.
“The usefulness of this review is that the authors importantly caveat that, with these greater benefits, comes a higher likelihood of adverse effects or harm, questioning their long-term compliance and suitability for some patients. Other drugs fare worse still, as the associated adverse effects outweigh the benefits or effectiveness. The implication that loss of lean mass is an adverse effect, however, needs to be contextualised. On average, body fat still accounts for 75% of the lost weight, which is comparable to body composition changes seen in other weight-loss interventions. Albeit, a greater overall weight loss will lead to a greater absolute loss of lean mass.
“The important message of this review is that long-term adherence to drugs is a challenge, and that many of these trials are of relatively short duration. Discontinuing or deprescribing these drugs is unlikely to lead to maintaining the benefits these drugs may have provided. Furthermore, we know that following drug cessation, weight regain is inevitable and may be accelerated. Without any other diet and lifestyle strategy in place for weight maintenance, or other support given, it would necessitate the continual use of drugs to maintain any benefit. This review highlights that even with the emergence of new drugs, pharmacotherapy alone is unlikely to be a viable long-term solution.”
Prof Naveed Sattar, Professor of Cardiometabolic Medicine/Honorary Consultant, University of Glasgow, said:
“This is an interesting paper, but the headline used in the accompanying press release is rather misleading, for reasons that are not entirely clear. Moreover, some of the conclusions drawn by the authors appear premature and insufficiently supported by the totality of the available evidence.
“Like many others, I wish we did not need anti-obesity medications and that our environment was far more conducive to healthy living. I have said so repeatedly. In the 1980s, obesity prevalence in the UK was approximately 6–7%, compared with around 30% today. However, given the scale of the current obesity epidemic (and the numbers suffering) and the substantial burden of disease associated with excess adiposity, it is important that evidence surrounding available treatments is interpreted accurately and comprehensively.
“With respect to cardiovascular health, we now have consistent evidence from multiple large-scale cardiovascular outcome trials of GLP-1 receptor agonists in type 2 diabetes1, including semaglutide (both injectable and oral formulations), dulaglutide, albiglutide and efpeglenatide, demonstrating reductions in major cardiovascular events compared with placebo. Indeed, the evidence has become so robust and consistent across trials and meta-analyses that clinical guidelines now recommend these agents for people with type 2 diabetes who also have established cardiovascular disease. Semaglutide has also been shown to reduce cardiovascular events in people without diabetes in the SELECT trial.
“For tirzepatide, the available evidence indicates non-inferiority to dulaglutide—a therapy with proven cardiovascular benefit—with respect to three-point major adverse cardiovascular events (myocardial infarction, stroke or cardiovascular death). Prespecified analyses2from the recently published SURPASS-CVOT further suggest that tirzepatide is likely superior to a putative placebo comparator in people with type 2 diabetes. Additional large-scale outcome trials with follow-up extending beyond two years are ongoing and will provide further clarity regarding the cardiovascular effects of newer agents.
“The discussion of quality of life also warrants greater nuance. While this paper suggests limited effects, several trials have reported improvements but few have considered analyses to account for ‘ceiling effects’ whereby improvements cannot be seen when QOL is not limited. Furthermore, most studies have relied on generic measures such as the EQ-5D, which may not fully capture the specific benefits associated with weight loss and improvements in physical functioning. Patient-reported outcome measures that are more closely aligned with obesity-related symptoms and functional limitations often demonstrate larger benefits, yet relatively few trials have incorporated such assessments. Consequently, this remains an important area for further research.
“That said, there is already considerable evidence that many individuals experience meaningful improvements in wellbeing that are not adequately captured by traditional patient-reported outcome measures. This may help explain why millions of people worldwide are willing to pay for these medications out of pocket, whereas comparatively few would do so for treatments such as statins or antihypertensive drugs.
“It is also worth noting the limitations acknowledged by the authors themselves. As stated in the paper: “Most trials had relatively short follow-up, with only a small number extending beyond two years, limiting conclusions about long-term safety, quality of life, and effects on cardiovascular and kidney outcomes.” Given this admission, strong conclusions regarding the absence of benefit in these domains seem difficult to justify.
“Importantly, the benefits of these medications extend well beyond cardiovascular disease, important as many people are increasingly living with many non-cardiovascular conditions linked to obesity. Trial evidence has demonstrated substantial reductions in the risk of developing type 2 diabetes—up to 93% in some trials—as well as clinically relevant improvements in obstructive sleep apnoea, reductions in osteoarthritis-related knee pain, lower blood pressure to levels seen with traditional blood pressure medications, improved lipid profiles, and better liver health, all findings which have or will influence relevant guidelines. Semaglutide has also shown clear kidney outcomes benefits in the FLOW trial3, while kidney outcome studies of newer agents are still ongoing.
“Moreover, evidence continues to emerge across a widening range of disease areas. Most recently, tirzepatide has demonstrated improvements in both psoriasis4 and psoriatic arthritis5 when added to existing biologic therapies. Numerous additional trials are underway in many other conditions, highlighting the potential broad therapeutic potential of these agents.
“Ultimately, while it would be far preferable to prevent obesity through effective public health, environmental and policy interventions, the reality is that millions of people are already suffering with obesity and experiencing its consequences. In this context, it is essential that headlines and conclusions accurately reflect the totality of the evidence. This requires careful consideration especially of large-scale, longer term outcome trials and high-quality phase 3 studies in differing conditions with adjudicated clinical endpoints.Systematic reviews that also aggregate many smaller trials, not set up to measure hard outcomes, cannot achieve that level of certainty.
“In my view, therefore, this new paper does not fully achieve balance. Indeed, even the accompanying editorial acknowledges that additional large-scale trial data are still awaited and will be necessary before more mature and definitive conclusions can be drawn on many aspects. As such, a more measured interpretation of the available evidence would have been preferable.”
1 https://pubmed.ncbi.nlm.nih.gov/40156846/
2 https://pubmed.ncbi.nlm.nih.gov/41940793/
3 https://pubmed.ncbi.nlm.nih.gov/38785209/
4 https://pubmed.ncbi.nlm.nih.gov/42139049/
5 https://pubmed.ncbi.nlm.nih.gov/41903163/
‘Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis’ by Kailei Nong et al. was published in The BMJ at 23:30 UK time on Wednesday 8 July 2026.
DOI: http://dx.doi.org/10.1136/ bmj-2026-372161
Declared interests
Marie Spreckley: “I have no personal financial interests, consultancy roles, advisory roles, speaker fees, stock ownership or honoraria from companies manufacturing incretin-based therapies. I am a researcher in obesity, nutrition and behavioural science. My research includes studies examining people’s experiences of incretin-based therapies.”
John Wilding: “reports consultancy / advisory board work for the pharmaceutical industry contracted via the University of Liverpool in the last 36 months (no personal payment) for Alnylam, Amgen, AstraZeneca, Boehringer Ingelheim, Cytoki, Kailera, Lilly, Menarini, Napp, Novo Nordisk, Pfizer, Prosciento, Response Pharmaceuticals, Rhythm Pharmaceuticals, Saniona, Shionogi; funding for clinical trials from Amgen, AstraZeneca and Novo Nordisk and personal honoraria / lecture fees from Abbvie, AstraZeneca, Boehringer Ingelheim, Medscape, Novo Nordisk and Menarini. He is past president of the World Obesity Federation, a member of the Association for the Study of Obesity, Diabetes UK, EASD, ADA, Society for Endocrinology and the Rank Prize Funds Nutrition Committee. From 2009-2024 he was national lead for the Metabolic and Endocrine Speciality Group of the UK NIHR Clinical Research Network.”
Liam Smeeth: “No conflicts.”
Adam Collins: “I declare no conflict of interest”
Prof Naveed Sattar: “has consulted for and/or received speaker honoraria from Abbott Laboratories, AbbVie, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gan & Lee, GlaxoSmithKline, Hanmi Pharmaceuticals, Janssen, Kailera, Mass Medicines, Menarini-Ricerche, Merck Sharp & Dohme, Metsera, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche, Sanofi, UCB Pharma and Verdiva Bio; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche. No shares in any medical areas.”
For all other experts, no reply to our request for DOIs was received.