In a session presented at the 2024 Heart in Diabetes Conference, Neha Pagidipati, MD, MPH, discussed weight change and its effects on cardiovascular complications.
Addressing various weight-loss mechanisms, researchers found that weight loss is associated with improved cardiovascular (CV) outcomes. However, when assessing weight-loss procedures—whether it be bariatric surgery, GLP-1 prescriptions, or intensive weight-loss activities—more research is needed to identify the best mode of accomplishing significant weight loss for better CV outcomes.
At the 2024 Heart in Diabetes Conference, Neha Pagidipati, MD, MPH, gave a presentation that detailed her ongoing research, which began with the fact obesity can exacerbate CV impact. With this knowledge, she highlighted studies addressing the ways in which weight loss is achieved and which procedures are the most beneficial in improving CV outcomes.1
With their goal of addressing the role of weight loss on CV outcomes, researchers first presented previous findings on the association between BMI and CVD.
A BMI of 40 or more is known to shorten life expectancy by about 10 years. It is also known to negatively affect overall mortality as well as all-cause mortality.1
Next, Pagidipati further presented researchers’ knowledge from previous studies and addressed her goals of identifying whether the relationship between obesity and CV outcomes is direct or indirect.
“But the question is: Is this a direct relationship or is this an indirect relationship? A lot of prospective cohort studies have suggested that [the] relationship is really mediated by the comorbidities associated with obesity, [like] hypertension, dyslipidemia, [and] diabetes,” she said. However, because most previous findings, and the studies that Pagidipati and her colleagues conducted, were not randomized, there is still a need for further randomized trials to confirm these findings.1
Pagidipati then explored the relationship between intentional and unintentional weight loss.
“Many observational studies have shown actually worse outcomes with weight loss. Maybe that's because we can't always tell in these observational studies when people are trying to lose weight versus not trying to lose weight. Unintentional weight loss, we can all kind of agree upon, is probably not a good thing, especially in an elderly population. And many of these studies also didn't take into account the physical fitness, which is also very important,” she said.1
In another previous study assessing the association between CV outcomes and obesity, researchers found that intentional weight-loss interventions were much more beneficial on CV outcomes than unintentional weight loss. However, researchers couldn’t come to a defined conclusion because the risk factors that led to weight loss in the unintentional weight loss group were unknown. This finding supports the hypothesis that unintentional weight loss can lead to worse CV outcomes while intentional weight loss can improve them.
Taking a deeper look at intentional weight loss, Pagidipati discussed another study that addressed physical activity regiments and their successful weight-loss mechanisms. While CV outcomes were all around improved in the physical activity cohort, most of the participants gained their weight back following the study period.
Pagidipati then presented 2 last methods of weight loss: bariatric surgery and glucagon-like peptide-1 receptor agonists (GLP-1s).
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One study observed patients who received bariatric surgery compared with a group that did not. Researchers found a 23% risk reduction for all-cause mortality, a 30% risk reduction for CV death, and an extended life expectancy of 3 years.1 Another study focusing on bariatric surgery found a 41% risk reduction in all-cause mortality and 62% risk reduction in heart failure.
And finally, one of the hottest topics in the weight-loss and prescription drug worlds, Pagidipati delved into GLP-1s and their potential effects on CV outcomes.
“Wegovy is now the first weight loss medication to also be approved to help prevent life-threatening [CV] events in adults with [CVD] and either obesity or overweight,” said John Sharretts, MD, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research, following Wegovy’s approval for treating CVD outcomes.2 “This patient population has a higher risk of cardiovascular death, heart attack, and stroke. Providing a treatment option that is proven to lower this cardiovascular risk is a major advance for public health.”
In Pagidipati’s research, she analyzed a study comparing a group taking 2.4 mg of semaglutide weekly with a placebo group. Similar to the study that led to Wegovy’s FDA approval, she found significant benefits of semaglutide on CV outcomes. However, further highlighting the uncertainty in weight loss’s relationship with CV outcomes, researchers were unsure if weight loss alone led to improved outcomes, or if GLP-s alone were responsible.1
“These are all things that are improved with weight loss and they improve as the amount of weight loss increases. So I still do believe that there is a significant benefit for our patients in promoting weight loss. And now we have many options for how we should do that,” continued Pagidipati.1
While she identified several uncertainties in the relationship between weight loss and CV outcomes, her research has increased findings on this relationship; it is just a matter of identifying the mechanisms of weight loss that can most significantly improve CV outcomes.
“So in conclusion, is obesity associated with poor cardiovascular outcomes? I would say yes. Directly or indirectly? Maybe a bit of both. Is weight loss associated with improved [CV] outcomes? I'm not totally sure. Lifestyle intervention: We have not proven that yet. With bariatric surgery, we think so… and then with [GLP-1RAs], perhaps yes… But there is so much more data on the way that we will find out hopefully soon,” concluded Pagidipati.1
And finally, addressing the question of whether providers should promote weight loss for their patients, Pagidipati said that it is absolutely necessary, despite any conflicting or uncertain results that accompanied her presentation.
