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A study published in the Lancet looks at semaglutide and cardiovascular health regardless of weight loss.
Dr Sonya Babu-Narayan, Clinical Director, the British Heart Foundation, and consultant cardiologist, said:
“These intriguing results demonstrate that the benefits of medications like semaglutide on heart health go beyond weight loss alone. But this leaves much unexplained. More research will be needed to unravel the other mechanisms of action behind the cardiovascular benefits beyond weight and fat loss, such as improvements in blood vessel health, control of blood pressure and blood sugar, or inflammation.
“While this is a very large study which followed patients for a long time, we can’t yet know the potential impact of sustained use of medications like these, especially in cardiovascular patients who are not living with overweight and obesity. Ongoing research must be better representative of all cardiovascular patients, including by involving more women and under-represented groups, and will be needed to shed light on any side effects that longer term use may have.
“So-called ‘weight loss drugs’ are becoming important heart medications. But if you have been prescribed them as part of your heart care, it’s important to remember that they are not a substitute for other things that keep our hearts and minds healthier for longer. This includes getting regular physical activity and trying to eat as healthy and nutritious a diet as possible, which will help to maximise your long-term heart health.”
Prof Azeem Majeed FMedSci, Professor of Primary Care and Public Health, Imperial College London, said:
“This is a high-quality study using data from over 17,000 patients in the SELECT trial to investigate how baseline and on-treatment changes in bodyweight and waist circumference relate to cardiovascular risk reduction with semaglutide. A key finding is that semaglutide’s 20% reduction in major adverse cardiovascular events is consistent across all baseline adiposity levels and is not linked to the amount of early weight loss. This finding challenges the belief that weight loss is the primary driver of benefit, showing instead that waist circumference reductions mediate only about a third of the effect on major adverse cardiovascular events.
“The authors adjusted appropriately for confounding factors such as age, sex, region, and baseline cardiovascular disease history. One limitation of the study is the trial’s focus on patients with BMI ≥27 kg/m² and prior cardiovascular disease, which means that the generalisability of the findings to lower-risk or non-obese groups is not known.
“The findings reinforce the use of semaglutide as a disease-modifying therapy for high-risk patients and not just as a weight-loss tool. In future, this may potentially lead to broadening the use of semaglutide beyond strict BMI cutoffs and encouraging its earlier use in cardiovascular disease prevention.”
Prof Tim Chico, Professor of Cardiovascular Medicine and Honorary Consultant Cardiologist, University of Sheffield, said:
“This paper re-analyses a previously published and important study called SELECT, in which people with a BMI over 27 who had already developed heart disease were given Semaglutide or placebo injections weekly. SELECT showed that Semaglutide reduced the chance of a further serious heart problem such as a heart attack or a stroke by around 20% (such events happened in 8.5% of people on placebo and 6% of people taking Semaglutide over about 4 years).
“This new analysis of the SELECT study finds that even people who were less over-weight, or who lost less weight than others, gained as much benefit as heavier people and those who lost more weight. This suggests the benefits of the drug are not only caused by causing weight loss. The biological reasons for these findings are unclear but often the most important thing is to know whether a drug prevents future heart attack and stroke, however it achieves this.
“The implications of this and other similar studies are profound. The average man or woman in the UK has a BMI over 27, so most people with heart disease are likely to benefit from adding Semaglutide to their existing drugs, which already usually include aspirin, statins, blood pressure lowering drugs, and other blood thinners. Evidence from this and other studies suggests we should consider giving these drugs to the very large number of people likely to get a meaningful benefit.
“Providing Semaglutide to everyone who would benefit will place a substantial burden on the NHS. Current guidelines limit use of drugs like Semaglutide to people with a BMI over at least 37.5 and often 40 but this study suggests this deprives a lot of people of the benefit of reduced future heart problems.
“There is sometimes an unhelpful either/or discussion about drugs versus behaviour change. The fact is we all need to do more and support others to reduce risk of heart disease via a healthier diet, more physical activity, not smoking, and knowing what our blood pressure and cholesterol levels are and when these might need treating with tablets. Drugs like Semaglutide are part of the solution but by no means the whole story. We should recognise that the need for such drugs points to longstanding failures to prevent the causes of heart disease such as obesity.
“This study shows we can do more to reduce future heart problems in people who have already survived a heart attack or stroke, but we must also do much more to stop people having these problems in the first place. This is everyone’s problem and we can all play a part in fixing it.”
Prof Naveed Sattar, Professor of Cardiometabolic Medicine/Honorary Consultant, University of Glasgow, said:
“The conclusion of this analysis – done reasonably well given the nature of the data – is not a surprise as it fits with what we know already from multiple GLP-1RA trials in people with type 2 diabetes, where some such medicines lowered heart attacks and stroke risks meaningfully despite negligible weight change. This means GLP-1RA medicines likely have some direct effects on tissues that slow development of plaques that cause heart disease. That said, weight loss is additionally beneficial for many other outcomes linked to obesity, and may add cardiovascular benefit over a longer time period. Much of this has been summarised already in a recent viewpoint paper https://pubmed.ncbi.nlm.nih.gov/39870097/.”
‘Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial’ by John Deanfield et al. was published in the Lancet at 23:30 UK time on Wednesday 22 October 2025.
DOI: 10.1016/S0140-6736(25)01375-3
Declared interests
Dr Sonya Babu-Narayan: “No conflicts.”
Prof Azeem Majeed: “I don’t have any conflicts of interest.”
Prof Tim Chico: “No conflicts of interest.”
Prof Naveed Sattar: “NS has consulted for and/or received speaker honoraria from Abbott Laboratories, AbbVie, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, GlaxoSmithKline, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Merck Sharp & Dohme, Metsera, Novartis, Novo Nordisk, Pfizer, Sanofi, and Roche; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche. No shares in any medical areas.”