Published on November 12, 2023, 12:48 am
Results from a groundbreaking clinical trial have revealed that a weight loss medication can potentially lower the risk of heart attack, stroke, or heart-related death in individuals with cardiovascular disease. This discovery has further fueled the enthusiasm among physicians for a burgeoning class of innovative medicines designed to combat obesity.
The drug in question, Wegovy, is part of a group of medications known as GLP-1 receptor agonists. In a recent trial presentation at the American Heart Association conference in Philadelphia, it was demonstrated that Wegovy could reduce the likelihood of another cardiovascular event by 20%. These results were obtained after confirming data from the full study dataset.
Dr. Ania Jastreboff, director of the Yale Obesity Research Center and one of the lead researchers involved in the trial, expressed optimism about the potential impact of treating obesity not only on weight loss but also on related conditions such as hypertension, high cholesterol, and type 2 diabetes. She emphasized that addressing obesity can significantly improve overall health outcomes.
However, one lingering question remains: Is Wegovy’s heart benefit solely due to weight loss or are there other mechanisms at play? Dr. Amit Khera from the University of Texas Southwestern Medical Center Dallas and Dr. Tiffany M. Powell-Wiley from the National Institutes of Health addressed this query in an editorial published alongside the study results in the New England Journal of Medicine. They stated that it remains unclear whether weight loss or other positive effects of GLP-1 receptor agonism contribute to Wegovy’s observed benefits.
Despite this uncertainty, both Khera and Powell-Wiley highlighted that we now have an expanding arsenal of treatment options to combat obesity and cardiometabolic risk factors. The recent FDA approval of Zepbound for obesity adds another drug to this growing toolkit, introducing competition for Wegovy.
Wegovy and Zepbound are both successors to medications used for managing type 2 diabetes that possess similar active compounds. Wegovy’s sister drug is Ozempic, and both drugs use semaglutide. Similarly, Zepbound utilizes tirzepatide, a compound shared by its predecessor Mounjaro. These medications are self-administered through weekly injections and work by mimicking hormones that stimulate insulin production, induce feelings of satiety, and reduce appetite. While semaglutide targets GLP-1, tirzepatide targets both GLP-1 and a hormone called GIP.
The trial showcased several positive outcomes among individuals using Wegovy over a two-year period. These participants were less likely to develop diabetes or prediabetes; experienced weight loss averaging 9.4% compared to 0.9% in the placebo group; achieved additional reductions in waist circumference; and demonstrated improvements in systolic blood pressure levels, C-reactive protein (a marker of inflammation), and triglycerides.
According to Dr. Steven Nissen from the Cleveland Clinic, these effects serve as evidence for the benefits of weight loss. He expressed excitement about finally having treatments that can make a substantial impact on patients’ weight. Many are now looking to tirzepatide as it has shown even greater levels of weight loss than semaglutide in clinical trials.
The Wegovy trial enrolled 17,604 individuals categorized as overweight based on their body mass index (BMI) of 27 or higher who had cardiovascular disease or symptoms like previous heart attacks, strokes, or peripheral artery disease indicating clogged arteries in the arms or legs. Importantly, participants did not have a history of diabetes since an earlier study revealed that treating diabetic patients with a GLP-1 drug significantly reduced their cardiovascular risk.
Among those taking Wegovy, only 6.5% experienced heart attacks, strokes, or died from heart-related causes during the trial compared to 8% in the placebo group. This translates to a 20% reduction in risk, as reported in August. These beneficial effects were evident even when accounting for other medications, such as statins for cholesterol management, which the majority of trial participants were already taking.
The trial results indicated that the most significant benefit was observed in reducing the risk of heart attacks (28%), followed by a reduced risk of strokes (7%). Although specific statistical significance for these measures was not provided, considering the inability to meet the threshold for cardiovascular death reduction, the overall 20% risk reduction remained highly statistically significant.
Regarding safety concerns, no new issues emerged during the study. However, fewer individuals continued taking semaglutide due to adverse effects compared to those receiving placebos. The most commonly reported adverse events included gastrointestinal problems such as nausea, vomiting, and diarrhea. Moreover, there was a slight increase in gallbladder-related disorders associated with Wegovy use compared to placebos.
It is worth noting that the average weight loss achieved in this trial (9.4%) was slightly lower than what previous studies using Wegovy demonstrated (around 15%). This distinction can be attributed to the current study’s focus on real-world