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Medscape
14-05-2025
- Health
- Medscape
Semaglutide May Cut Cardiovascular Risk Before Weight Loss
MÁLAGA, Spain — Semaglutide (Wegovy) is associated with a 41% reduction in the risk for major adverse cardiovascular events (MACEs) within 6 months of initiation — well before patients achieve substantial weight loss or reach the full 2.4 mg weekly dose — according to new data from the SELECT trial. 'The cumulative incidence of MACEs during the first 6 months showed a hazard ratio of 0.59,' said Donna Ryan, MD, professor emerita at Pennington Biomedical Research Center in Baton Rouge, Louisiana. Ryan, a member of the SELECT steering committee, presented the data alongside Jorge Plutzky, MD, director of Preventive Cardiology at Brigham and Women's Hospital and professor of medicine at Harvard Medical School, Boston. The findings were presented at the European Congress on Obesity (ECO) 2025. Early Benefits The early cardiovascular (CV) benefit emerged before participants reached the target dose of semaglutide or experienced meaningful weight reduction. The hazard ratio (HR) of MACEs for patients receiving semaglutide was 0.63 (95% CI, 0.41-0.95) during the first 3 months. 'The HRs for MACEs were below 1 before the weight loss started and before participants reached the top dose,' Ryan said. 'Almost immediately, the risk is less on semaglutide than on placebo.' The first statistically significant reduction in MACEs occurred by day 20 after randomization, with sustained significance evident by day 86. In the first 6 months, 67 MACEs occurred in the semaglutide arm vs 113 in the placebo arm (HR, 0.59; 95% CI, 0.44-0.80). The researchers observed a 53% reduction in CV deaths (14 deaths with semaglutide vs 30 deaths with placebo) and a 43% reduction in nonfatal myocardial infarction. The reduction in nonfatal stroke was not statistically significant (HR, 0.87; 95% CI, 0.47-1.58). Design and Execution These new findings add to results from the main SELECT trial, which previously was reported by Medscape Medical News . That trial found a 20% reduction in MACEs over nearly 40 months in patients with overweight or obesity and established CV disease (CVD; HR, 0.80; 95% CI, 0.72-0.90; P < .001). 'The design and precision of execution give us confidence in the results,' Ryan said. SELECT enrolled 17,604 participants aged 45 years or older with overweight or obesity (body mass index ≥ 27) and established CVD, which was defined as prior myocardial infarction, stroke, or symptomatic peripheral artery disease. Eligible participants did not have type 2 diabetes, although two-thirds of participants had prediabetes. Participants were randomly assigned to once-weekly subcutaneous semaglutide or placebo (titrated to 2.4 mg by week 16) alongside standard-of-care treatments including statins, antihypertensives, and antiplatelet therapy. 'This was not a weight loss study,' Ryan emphasized. 'We thought that the drug itself might have properties beneficial to cardiovascular outcomes apart from weight loss.' CV Benefits First In the first 12 months, semaglutide was associated with a 9% reduction in body weight. However, this degree of weight loss was not yet apparent when the early CV benefit emerged. At week 4, change in body weight was −1.1% for patients on semaglutide compared with placebos (95% CI, −1.2 to −1.1). By week 12, the difference was −3.6% (95% CI, −3.7 to −3.5). To explore whether weight loss explained the early benefit, investigators compared daily hazard ratios for MACEs with average weight change over time. The dissociation between the curves suggested that the early CV benefit may occur independently of weight loss. Potential Mechanisms Asked to comment by Medscape Medical News , Jason Halford, PhD, head of the School of Psychology at the University of Leeds, Leeds, England, and past president of the European Association for the Study of Obesity, London, England, said that the results were surprising. 'This [study] suggests that [the benefits are] not mediated by weight loss and that there must be some other mechanism underpinning it,' Halford said. 'Possibly a reduction in inflammation, because obesity is an inflammatory disease, and it's a component of many other diseases.' These findings may inform early treatment decisions in patients with obesity and CVD, even before significant weight loss has been achieved. Halford suggested that the findings could have implications for CV medicine. 'Of course, they are managing CVD with other therapies, and it would be interesting to compare not one antiobesity drug with another but to see how this impacts existing treatments for CVD. It might be preferable to use one drug to treat two things, for example.' Halford also noted that as new antiobesity drugs and combinations of mechanisms emerge, comparisons should extend beyond weight loss to include CV outcomes. 'These early data shift the narrative. We knew the long-term benefits, but the short-term effect is unexpected.'
Yahoo
13-05-2025
- Health
- Yahoo
Study: Wegovy cuts heart disease risk even before people shed weight
The weight-loss drug Wegovy slashes the risk of heart disease even before people shed many pounds, data suggests. The drug, which contains the active ingredient semaglutide, works by reducing food cravings and is also available for people with a high BMI. New data, presented by the manufacturer Novo Nordisk, shows Wegovy can protect against heart disease in the earliest stages, while also working to dramatically cut the risk of having a heart attack, stroke or early death in high-risk patients. Analysis of a clinical trial found it reduced the risk of having a heart attack, stroke or heart disease death by 37% in people with obesity and cardiovascular disease within the first three months of treatment. Furthermore, within six months of treatment, Wegovy reduced the risk of cardiovascular death by 50% and cut the risk of needing urgent treatment due to heart failure. Analysis of the Select trial data also found Wegovy protected against heart disease even before people had lost clinically meaningful amounts of weight (considered as less than 5%). This suggests Wegovy's protection against heart disease is not only related to its effect on driving weight loss, researchers said. The effect was also found before people had even moved on to the 2.4mg maintenance dose of the drug, which is a GLP-1 receptor agonist. Dr. Jorge Plutzky, lead study author and director of preventive cardiology at Brigham and Women's Hospital at Harvard Medical School in the US, said: "Semaglutide 2.4mg is the only GLP-1 to have shown these early, rapid effects on heart disease, with benefits seen in the order of months, not years - underscoring its important role in clinical practice." He added: "Our findings reveal an early separation in the treatment effect of semaglutide that occurs even without a significant amount of weight lost and prior to full semaglutide titration. "More research is needed to understand the mechanisms through which semaglutide produces these early clinical benefits, but they may include the drug's positive effects on reducing inflammation, blood sugar, blood pressure, direct effects on the heart and blood vessels, early dietary changes, or an interaction among these or other responses." The Select trial is a randomised, double-blind trial looking at semaglutide 2.4mg versus placebo for the prevention of heart attacks, strokes and early death in people with established cardiovascular disease who are overweight or have obesity. Patients in the trial were already on other drugs such as for cholesterol and blood pressure, suggesting semaglutide had benefits on top of these. The study was presented at the European Congress on Obesity in Malaga.
