Full data from the longest-ever study of the obesity drug Wegovy (semaglutide) show that it helps people lose weight and keeps them down over a minimum of four years. Full analysis of the completed 2023 SELECT trial also showed that Wegovy has the potential to decrease the risk of heart disease, a finding that could have it covered by a number of insurance plans. The groundbreaking new study involving this many volunteers who’ve taken Wegovy—to include it’s safe and successful in every demographic, from sex to race or ethnicity, body size, and even geographic region.
The second big finding was that Wegovy can improve cardiac health in subjects who didn’t have a real weight loss. Dr. Harlan Krumholz, a professor of medicine at the Yale School of Medicine and the incoming editor in chief of the Journal of the American College of Cardiology, said the new findings should shift the way doctors think about semaglutide away from the view of the drug as something you’d expect to get out of the medicine cabinet in terms of a weight loss medication. The takeaway might be that in the future, Wegovy will be more famous for its benefits in cardiac health than as an obesity treatment.
Consistent with this interpretation, a preprint secondary analysis of one of the JACC studies found that Wegovy can help people with heart failure and obesity independent of weight loss. Dr Krumholz noted that this added on to the idea of Wegovy as a treatment for heart failure as well as obesity.
In a recent poll by Kaiser Family Foundation, around 6% of the respondents reported taking such drugs like Wegovy, Ozempic, or Mounjaro, which are GLP1 receptor agonist drugs. According to Novo Nordisk, the company that fabricates Wegovy, almost 25,000 new patients start taking the drug weekly.
Oral Wegovy and Long-Term Efficacy
The data for the GSM was derived from the SELECT study, which was performed on more than 17,600 individuals who were using Wegovy from 2018 to 2021. The findings of the study have been published last week by JACC and represent one of several sub-papers examining various aspects of the trial. The analysis showed that the people who received Wegovy for four years were losing weight within about 65 weeks and keeping it off for as long as they were followed. This duration is considerably longer than that in previous studies.
The participants lost 10% of their initial body weight on average, over these four years, a bit lower in comparison to similar studies where the average was 15%. Hence, this could perhaps explain why there is such a difference, since the participants did not take the maximum dose of Wegovy and were not even required to change their lifestyle, said Dr. Donna Ryan, emeritus professor at Pennington Biomedical Research Center and senior author of the research.
After two years of the study, 12% of those taking Wegovy had achieved a “healthy” BMI below 25 kg/m², where only 1% on the placebo achieved this. Besides, over half of the patients no longer had obesity by their BMI classification.
Reorientation: BMI and Wider Ramifications
The researchers in this study also sorted the results into demographic subgroups, such as age, sex, initial BMI, race, and ethnicity, and found weight loss to be consistent across all. Notably, when the participants were between 27 and 30 BMI (overweight), the amount of lost weight was less than among those who started with a higher BMI. According to Dr. Ryan, this might be due to a mathematical limitation—those closer to their weight loss plateau would have proportionately less weight to lose.
Dr. Ryan also indicated that this change in BMI isn’t sufficient to measure if the drug is successful on its own. Variations in glucose and A1c levels, blood pressure, lipid levels, mobility, and body satisfaction are equal determinants of drug success. Since it’s overwhelming to estimate whether Wegovy would keep off weight for longer, Dr. Ryan herself expressed conviction that keeping weight loss for four years is a minimal groundwork for hope.
Cardiovascular benefits beyond weight loss
The SELECT trial demonstrated a 20% reduction in adverse cardiovascular events, which include heart attacks, strokes, and deaths due to cardiovascular diseases. The new analysis and the study in JACC validated this finding. In the JACC study, investigators reported significant reduction in an important biomarker used in the diagnosis and prognosis of heart failure among obese patients with heart failure taking semaglutide. Among people who had the most of this type of biomarker, semaglutide improved heart health equivalently to the other standard medications for the heart.
At the European Congress on Obesity, it was revealed that an analysis of SELECT data by University College London Professor John Deanfield—which was published at the meeting—demonstrated that semaglutide was associated with cardiovascular protection independent of the BMI of participants. Even among people who lost less than 5% of their body weight while on semaglutide, major cardiovascular events were lesser compared to the placebo group.
Mechanisms of Improvement in Cardiovascular Diseases
Various mechanisms have been postulated for the improvements in cardiovascular outcomes with weight loss among individuals with obesity. Lowering blood pressure through weight loss means a lesser workload for the heart. But this trial suggests that any cardiovascular benefit arising from semaglutide is possibly unrelated to weight reduction and is likely through other mechanisms—lowering levels of inflammation, protecting the kidneys, and reducing fat around the heart.
Dr. Krumholz called for more regular measurement of cardiovascular risk factors, including blood pressure, cholesterol, and glucose among patients taking semaglutide. The big “through line” is: aside from the newer findings on cardiovascular benefits, it seems there’s little new information here that should make patients want to stop taking semaglutide, relative to prior weeks.
Insurance and Wider Coverage
In March, the FDA cleared a new indication for Wegovy to reduce the risk of heart attack and stroke in people with heart disease who have overweight or obesity. Then, this month, Medicare officials said they would pay for Wegovy in people with a prior heart attack, stroke or peripheral artery disease. He said with the kind of evidence emerging from the SELECT and JACC studies, semaglutide would be deserving of wider insurance coverage, making the medications accessible due to their enormous health benefits.
Dr. Veronica Johnson is assistant professor of Medicine at the Northwestern University Feinberg School of Medicine. She believes that semaglutide is going to lead to even more health benefits beyond direct weight loss. She explained how research indicates that patients might not need the highest dose to achieve meaningful health improvement – findings she hoped would “give prescribers more flexibility in their prescribing practices” independent of insurance determinations which are often based on the dose.
This will, in turn, establish through evidence the long-term effectiveness of Wegovy for weight loss and major cardiovascular event prevention, which is sorely needed for the revival of its importance in managing these two diseases.