Unraveling the Heart Benefits of Wegovy: Weight Loss or Another Factor?
A groundbreaking clinical trial revealed that Wegovy, a weight loss medication, has the potential to significantly lower the risk of heart attack, stroke, and heart-related deaths in individuals with cardiovascular disease This exciting discovery has further fueled the enthusiasm of physicians for this rapidly growing class of innovative medicines Sign up for CNN Health's weekly newsletter to stay updated
Results from a groundbreaking clinical trial this summer indicated, for the first time ever, that a medication administered solely for the purpose of weight loss could potentially diminish the likelihood of heart attack, stroke, or death related to heart ailments in individuals afflicted with cardiovascular disease. This discovery has further enhanced the enthusiasm of medical practitioners for an already burgeoning category of innovative drugs.
Wegovy (semaglutide 2.4mg)
Courtesy Novo Nordisk
The trial revealed that Wegovy, a weight-loss medication developed by Novo Nordisk, has provided the greatest benefit ever observed for patients with the most prevalent type of heart failure. The results, which were presented at the American Heart Association conference in Philadelphia, demonstrated that Wegovy reduced the risk of subsequent cardiovascular incidents by 20%.
"Consider an envisioned future where we not only address obesity but also effectively treat the accompanying obesity-related conditions, such as hypertension, high cholesterol, and type 2 diabetes," stated Dr. Ania Jastreboff, director of the Yale Obesity Research Center, who played a role in the trial. During a briefing on Friday, she further emphasized, "By treating obesity, we indisputably enhance health outcomes."
However, a pivotal question regarding the initial findings still remains unanswered: Is the cardiovascular benefit derived from Wegovy solely attributed to the amount of weight individuals shed while using the medication, or does Wegovy exert additional effects as well?
Dr. Amit Khera from the University of Texas Southwestern Medical Center Dallas and Dr. Tiffany M. Powell-Wiley from the National Institutes of Health highlighted in an editorial published in the New England Journal of Medicine that the trial findings from the study called Select are still unclear regarding the extent to which they were influenced by weight loss, reductions in risk factors, or other beneficial mechanisms of GLP-1 receptor agonism. However, they emphasized that we are now entering a new era in the management of obesity and cardiometabolic risk, with a wide range of options available.
The tool chest grew this week as the US Food and Drug Administration approved Zepbound, a drug from Eli Lilly, to treat obesity. Zepbound will directly compete with Wegovy, another drug for obesity. Both medications are derived from drugs used to treat type 2 diabetes. Wegovy's sister drug is Ozempic, and both Zepbound and Wegovy utilize semaglutide as their active compound. The drugs are administered via a self-administered shot once a week.
GLP-1 receptor agonists, such as semaglutide, mimic hormones that stimulate insulin production, promote feelings of fullness, and reduce appetite. Tirzepatide, the active compound in Zepbound, targets both GLP-1 and a hormone called GIP.
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The trial revealed significant benefits for those using Wegovy after a two-year period. Compared to the placebo group, Wegovy users were less likely to develop diabetes or prediabetic blood sugar levels. They also experienced a notable 9.4% reduction in body weight, as opposed to the placebo group's 0.9% decrease. In addition, Wegovy users saw a decrease in waist circumference by an extra 6.6 centimeters compared to the placebo group. Furthermore, they showed greater reductions in systolic blood pressure, C-reactive protein (a marker of inflammation), and triglyceride levels.
Sponsored by Novo Nordisk, the study involved 17,604 individuals with a body mass index of 27 or higher, indicating they were overweight. These participants also had cardiovascular disease, evidenced by a previous heart attack or stroke, or symptoms of peripheral artery disease (blocked arteries in the limbs).
Participants in the study did not have a prior history of diabetes. A previous trial had revealed that treating individuals with diabetes using a GLP-1 drug called Ozempic effectively decreased their risk of cardiovascular complications.
Findings from the Wegovy trial demonstrated that out of 8,803 individuals taking the medication, 569 individuals, or 6.5%, experienced a heart attack, stroke, or death from heart-related causes. In comparison, 701 out of 8,801 individuals receiving a placebo, or 8%, experienced the same outcomes. The discrepancy in these rates is what equates to the 20% benefit that was reported in August.
The trial participants, 90% of whom were taking statins to reduce cholesterol, along with other standard heart medications, realized the benefits early on. "The disparities in rates between the two treatment groups became apparent within the initial months of treatment," stated Dr. A. Michael Lincoff, leader of the trial at the Cleveland Clinic.
An Ozempic (semaglutide) injection pen is seen on a kitchen table in Riga, Latvia on 06 August, 2023. (Photo by Jaap Arriens/NurPhoto via Getty Images)
Jaap Arriens/NurPhoto/Getty Images
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The 20% reduction was achieved through a combination of three measures. However, when analyzed individually, not all of them showed statistical significance. The first measure focused on death from cardiovascular causes, and although there seemed to be a 15% decrease in risk with Wegovy, the results were not statistically significant, indicating that they are not as reliable.
The most significant benefit was observed in the prevention of heart attacks, with a risk reduction of 28%. Strokes were also reduced by 7%. Unfortunately, it is unclear whether these measures reached statistical significance, as the researchers did not calculate those values after the initial finding on deaths fell short of the required threshold. Nevertheless, the overall result of a 20% risk reduction is statistically robust.
No new safety concerns were discovered in the study. However, it was found that more individuals discontinued the use of semaglutide compared to placebo due to adverse events. The most commonly reported adverse events were gastrointestinal disorders such as nausea, vomiting, and diarrhea. Additionally, there was a minor increase in gallbladder-related issues with Wegovy compared to placebo.
The weight loss observed in the trial, which was 9.4%, was lower than the average weight loss seen in other studies of Wegovy, which showed an average weight loss of around 15%. It is important to note that this trial did not specifically focus on weight management, which typically involves modifications in diet and exercise along with close monitoring. Instead, the trial aimed to simulate the treatment approach for cardiovascular disease in real-world scenarios.
In this study, it should be noted that not all participants received the highest dose of Wegovy. The dosage of the medication was adjusted according to any reported side effects.
Regarding the trial's benefits, Lincoff highlighted that the heart benefits were observed earlier in the study compared to significant disparities in weight loss between Wegovy and the placebo. He further emphasized that even individuals who initially weighed less experienced the same level of benefit.
I believe that many of us understand that weight loss is a part of this, but I believe that oversimplifies a highly intricate molecule and a complex receptor that exists in various tissues. I don't think it's as straightforward as that. That's one of the reasons why I don't consider weight loss alone as the substitute; we need to examine the mechanism behind the weight loss."
Furthermore, Jastreboff mentioned, "It is possible that it is a combination of both factors."
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The study did not answer a few important questions. It only examined the risk of heart issues in individuals who already had cardiovascular disease. It is crucial to determine whether the drug could also be beneficial for those who have not experienced a cardiac event. Additionally, the trial had imbalances in terms of race and gender. Only 3.8% of participants were Black, and 28% were women.
These findings are expected to lead to a higher demand for the drug, which is already limited in supply. Moreover, there is potential for insurance coverage to be improved, as it is currently inconsistent. Before insurance, Wegovy costs $1,349 per month.
Based on these findings, Khera and Powell-Wiley stated in their editorial that although the drug could potentially benefit millions more patients, its current pricing for GLP-1 receptor agonists poses a significant cost barrier, rendering the treatment inaccessible for many individuals.
